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WORKS   OF    DR.    M.    H.    FISCHER 

PUBLISHED    BY 

JOHN  WILEY  &  SONS. 


The  Physiology  of  Alimentation. 

Large   i2mo,  viii  +  348  pages,    30    figures,   cloth, 
$2  00  net. 


TRANSLATION. 


Physical  Chemistry  in  the  Service  of  Medicine. 

Seven  Addresses  by  Dr.  Wolfgang  Pauli,  Privat- 
docent  in  Internal  Medicine  at  the  University  of 
Vienna.  Authorized  Translation  by  Dr.  Martin 
H.  Fischer,     iamo,  ix+156  pages,  cloth,  $1  25  net 


THE 


Physiology    of  Alimentation 


DR.    MARTIN    IT.    FISCHER 

Profasor  of  Pathology  in  the  Oakland  College  of  Medicine 


FIRST    EDITION 
FIRST    THOUSAND 


NEW    YORK 

JOnN   WILEY   &   SONS 

London:    CHAPMAN  &  HALL,   Limited 

1907 


Copyright,  1907 

BY 

MARTIN  H.   FISCHER 


ROBERT   DRUMMOND,   PRINTER,   NEW  YORK. 


TO 

C.    R.    F. 


PREFACE. 


The  following  pages  are  intended  primarily  for  those  whose 
interests  lie  in  physiology  as  a  science  contributory  to  medi- 
cine. In  no  sense  do  they  constitute  a  complete  review  of 
the  physiology  of  the  alimentary  tract,  but  only  such  an  out- 
line of  the  subject  as  I  have  been  in  the  habit  of  presenting  to 
my  students.  This  volume  is  intended  to  be  the  first  of  a 
series  of  monographs  dealing  with  various  phases  of  physi- 
ology. Some  effort  has  been  made  to  embody  a  few  of  the 
ideas  that  modern  physiological  investigations  have  brought 
with  them,  but  how  long  even  these  recent  conceptions  will 
stand  cannot  be  foreseen.  My  anticipations  will  be  fulfilled 
if  the  volume  serves  as  a  weather-vane  which  indicates  for 
the  time  being  the  direction  in  which  the  wind  is  blowing. 

I  am  indebted  to  a  number  of  my  friends  for  suggestions. 
To  two  of  these  I  would  express  my  especial  appreciation — 
to  Dr.  Charles  S.  Arnold  of  the  Oakland  College  of  Medi- 
cine, and  to  Miss  Marian  O.  Hooker  of  the  University  of 
California. 

Martin  H.  Fischer. 

Oakland  College  of  Medicine, 
January,  1907. 


TABLE  OF  CONTENTS. 


CHAPTER  I. 

The  Mechanical  Phenonema  of  Alimentation.  Page 

1.  The  General  Functions  of  the  Alimentary  Tract 1 

2.  Mastication 2 

3.  Deglutition 3 

4.  The  Movements  of  the  Stomach 6 

5.  The  Passage  of  Different  Foodstuffs  from  the  Stomach — 

The  Opening  and  Closing  of  the  Pyloric  Sphincter. .  16 

CHAPTER  II. 

The  Mechanical  Phenomena   of  Alimentation — (Continued). 

6.  The  Movements  of  the  Small  Intestine 22 

7.  The  Movements  of  the  Large  Intestine 29 

8.  Defalcation 35 

9.  The  Movement  of  Food  through  the  Alimentary  Tract  as 

a  Whole 36 

10.  The  Nervous  Control  of  the  Movements  of  the  Alimentary 

Tract 41 

11.  On  the  Action  of  Saline  Cathartics 46 

12.  The  Fate  of  Nutrient  Enemas 52 

CHAPTER  III. 

The  Juices  Poured  out  upon  the  Food  and  Their  Chemical  Con- 
stituents. 

1.  The  Saliva 62 

2.  The  Gastric  Juice 66 

3.  The  Pancreatic  Juice 68 

4.  The  Bile 70 

5.  The  Intestinal  Juice 73 

v 


Vl  TABLE  OF   CONTENTS. 

CHAPTER  IV. 

Ferments  and  Fermentation.  page 

1.  Organic  Ferments . 79 

2.  Inorganic  Ferments. 93 

CHAPTER  V. 

The  Action  op  the  Enzymes  Found  in  the  Human    Alimentary 
Tract. 

1 .  Amylase 99 

2.  Maltase 104 

3.  Caseinase 110 

CHAPTER  VI. 

The  Action  op  the  Enzymes  Found  in  the  Human  Alimentary 
Tract — (Continued). 

4.  Acid-proteinase 114 

5.  Alkali-proteinase 122 

CHAPTER  VII. 

The  Action  of  the  Enzymes  Found  in  the  Human  Alimentary 
T  ract —  (Continued ) . 

6.  Quantitative  Estimation  of  the  Proteinases 129 

7.  Antiproteinase 133 

8.  Why  the  Alimentary  Tract  Does  not  Digest  Itself 135 

9.  The  Reversible  Action  of  the  Proteinases 140 


CHAPTER  VIII. 

The  Action  op  the  Enzymes  Found  in  the  Human  Alimentary 
Tract —  (Concluded). 

10.  Protease 146 

11.  Lipase 149 

12.  Sucrase 153 

13.  Lactase 157 

14.  Arginase 158 

CHAPTER  IX. 

The  Bacteria  of  the  Alimentary  Tract 160 


TABLE  OF  COX  TENTS.  vii 

CHAPTER  X. 

The  Regulation  of  Salivary  Secretion..  paob 

1.  Salivary  Fist  viler .  177 

2.  The  Relation  of  the  Nerves  to  Salivary  Secretion 178 

3.  The  Reflex  Secretion  of  Saliva 182 

4.  On  the  Nature  of  Salivary  Secretion- 186 


CHAPTER  XI. 

The  Regulation  op  Gastric  Secretion. 

1.  Gastric   Fistulsc 188 

2.  Effect  of  Diet  on  Gastric  Secretion 192 

3.  Relation  of  the  Nervous  System  to  Gastric  Secretion .  .  .  200 

4.  The  Appetite  as  an  Excitant  of  Gastric  Secretion 203 

5.  Physiological  Importance  of  the  Appetite  Juice 205 

6.  Other  Excitants  of  Gastric  Secretion 208 

7.  Gastric  Secretin 211 


CHAPTER  XII. 

The  Regulation  of  Pancreatic  Secretion. 

1.  Pancreatic  Fistulse 215 

2.  Effect  of  Diet  on  Pancreatic  Secretion 216 

3.  Relation  of  the  Nervous  System  to  Pancreatic  Secretion.   222 

4.  The  Normal  Excitants  of  the  Pancreas 224 

5.  Pancreatic  Secretin 227 

6.  Significance  of  the  Physiology  of  the  Gastric  and  Pan- 

creatic Secretions 230 

7.  On  the  Adaptation  of  the  Digestive  Glands  to  the  Char- 

acter of  the  Food 234 


CHAPTER  XIII. 

The  Regulation  of  the  Biliary  and  the  Intestinal  Secretions. 
The  Functions  of  the  Bile. 

1.  Secretion  of  the  Bile 237 

2.  Physiological  Importance  of  the  Bile 23S 

3.  Regulation  of  the  Intestinal  Secretion 243 

4.  Enterokinase 246 


viii  TABLE  OF  CONTENTS. 

CHAPTER  XIV. 

The  Alimentary  Tract  as  an  Absorptive  System.  page 

1.  The  Problem  of  Absorption 249 

2.  The  Physical  Character  of  the  Foodstuffs 251 

3.  Membranes 254 

4.  The  Forces  Active  in  Absorption 257 

CHAPTER  XV. 

The  Alimentary  Tract  as  an  Absorptive  System — (Continued). 

5.  The  Absorption  of  Water 262 

6.  Lipoidal  Absorption . 268 

7.  The  Absorption  of  Salts 274 

CHAPTER  XVI. 

The  Alimentary  Tract  as  an  Absorptive  System — (Continued). 

8.  The  Absorption  of  Carbohydrates 282 

9.  The  Absorption  of  Fats 287 

CHAPTER  XVEI. 

The  Alimentary  Tract  as  an  Absorptive  System — (Concluded). 
10.  The  Absorption  of  Proteins 299 

CHAPTER  XVIII. 

The  Alimentary  Tract  as  an  Excretory  System. 

1.  General  Considerations,  Clinical  and  Experimental 311 

2.  The  Character  of  the  Alimentary  Contents:  The  Fa3ces.. .  317 


PHYSIOLOGY  OF  ALIMENTATION. 


CHAPTER  I. 
THE  MECHANICAL  PHENOMENA  OF  ALIMENTATION. 

i.  The  General  Functions  of  the  Alimentary  Tract. — 
Under  the  functions  of  the  alimentary  tract  are  included  all  the 
functions  of  the  hollow  tube  which  begins  with  the  mouth 
and  ends  with  the  anus,  together  with  certain  of  those  of 
the  glands  which  pour  their  secretions  into  this  tube.  The 
changes  which  the  food  undergoes  in  its  passage  through 
this  tube  are  in  part  purely  mechanical — such  for  example 
as  are  the  consequence  of  mastication  or  the  movements 
of  the  stomach — in  larger  part,  however,  chemical.  As  an 
example  of  the  latter  may  be  mentioned  the  conversion  in 
the  stomach  of  albuminous  bodies  such  as  egg  white  into 
the  chemically  less  complex  peptones.  Yet  these  chemical 
changes  are  frequently  associated  with  physical  or  physico- 
chemical  ones  which  from  a  physiological  standpoint  may 
at  times  be  quite  as  important  as  the  chemical  changes 
themselves. 

We  can  classify  the  various  substances  which  serve  as 
food  under  the  general  headings  of  proteins,  carbohydrates, 
fats,  and  inorganic  substances.  Under  the  first  heading 
fall,  for  example,  the  lean  meats,  the  white  of  egg,  etc., 
while  the  chief  representatives  of  the  carbohydrates  are 
the  starches  and  sugars  which  we  consume.     The  fats  are 


2  PHYSIOLCGY  OF  ALIMENTATION. 

in  pari,  of  animal,  in  part  of  vegetable  origin.  Among  the 
vegetable  fats  are  the  cottonseed  and  olive  oils,  while  familiar 
examples  of  animal  fats  are  found  in  butter,  cream,  and 
the  fats  of  fat  meat.  Water  makes  up  the  bulk  of  the 
inorganic  material  which  we  consume.  Among  the  other 
inorganic  constituents  of  our  food  are  the  all-important 
salts,  which  come  to  us  in  part  as  natural  components  of 
our  diet,  in  part  as  condiments,  or  as  constituents  of  the 
so-called  mineral  waters. 

Representatives  of  all  these  classes  are  found  in  the  or- 
dinary mixed  diet,  and  no  diet  is  sufficient  for  man  for  any 
length  of  time  unless  it  contains  representatives  of  all  these 
classes.  This  mixed  diet  enters  the  alimentary  tract,  some- 
times finely  divided,  sometimes  in  a  state  of  coarse  division. 
Some  of  the  constituents  of  the  food  may  be  in  suspension 
or  in  solution  in  water.  At  times  the  food  is  cooked,  at 
other  times  uncooked,  and  in  this  state  is  started  on  its 
way  through  the  alimentary  tract.  The  alimentary  tract 
takes  up  or  absorbs  from  this  heterogeneous  mass  which 
enters  the  mouth  certain  constituents  of  the  food  either 
in  the  condition  in  which  they  are  consumed  by  the  indi- 
vidual or  after  they  have  been  acted  upon  by  the  secre- 
,  tions  of  the  alimentary  tract.  Besides  altering  the  physical 
and  chemical  constitution  of  the  food  the  alimentary 
tract  therefore  acts  as  an  absorptive  system.  Interestingly 
enough,  however,  it  also  acts  as  an  excretory  system.  All 
these  various  functions,  not  only  the  elaboration  of  the 
food  by  physical  and  chemical  means,  but  also  those  of 
absorption  and  excretion,  are  included  under  the  general 
caption,  alimentation. 

We  shall  now  take  up  these  functions  separately,  direct- 
ing our  attention  first  to  the  mechanical  phenomena  which 
are  associated  with  the  journey  of  the  food  through  the 
alimentary  tract. 

2.  Mastication. — The  articulation  of  the  inferior  maxillary- 
bone  with  the  skull  allows  of  a  variety  of  movements  all 


MECHANICAL  PHENOMENA.  3 

of  which  arc  under  the  control  of  the  will.  The  lower  max- 
illary bone  may  he  dropped  and  raised,  may  be  thrown 
forward  and  drawn  backward,  and  may  be  moved  from 
side  to  side.  Ordinary  mastication  in  the  human  being  is 
a  combination  of  all  these  movements.  The  lower  jaw 
is  lowered  and  raised  in  the  ordinary  biting  movements,  and 
moved  from  side  to  side  when  the  food  is  being  chewed. 
Combined  with  both  of  these  may  be  more  or  less  well-marked 
forward  and  backward  movements  of  the  jaw.  The  food 
is  kept  between  the  teeth  and  the  act  of  mastication  made 
more  effective  by  the  simultaneous  action  of  the  muscles 
of  the  tongue,  cheeks,  and  lips.  The  cheeks,  and  more 
especially  the  tongue,  aid  also  in  gathering  together  the 
food  in  the  mouth  and  forming  it  into  a  bolus  preparatory 
to  the  act  of  swallowing. 

The  muscles  concerned  in  the  movements  of  the  lower 
jaw  are  the  following.  The  masseter,  temporal,  and  internal 
pterygoid  raise  the  jaw.  The  digastric  is  the  chief  depressor 
of  the  lower  maxilla,  aided  at  times  by  the  mylo-hyoid  and 
genio-hyoid  muscles.  The  jaw  is  thrown  forward  by  the 
simultaneous  contraction  of  the  external  pterygoids.  When 
these  muscles  move  singly,  side-to-side  movements  are  pro- 
duced. The  jaw  is  retracted  by  contraction  of  the  tem- 
poral muscle.  The  muscles  of  mastication  receive  their 
nerve  supply  from  the  inferior  maxillary  division  of  the 
fifth  cranial  nerve  with  the  exception  of  the  genio-hyoid, 
which  is  supplied  by  the  hypoglossal  nerve. 

3.  Deglutition. — It  seems  to  be  essential  for  the  proper 
performance  of  the  act  of  deglutition  that  the  mass  to  be 
swallowed  be  moist.  Dry  material  can  either  not  be  swallowed 
at  all  or  at  best  with  difficult}'.  While  certain  substances 
may  therefore  be  swallowed  immediately,  it  is  necessary  for 
others  that  they  remain  in  the  oral  cavity  until  they  have 
been  thoroughly  mixed  with  saliva,  or,  in  people  of  improper 
dietary  habits,  until  they  have  been  moistened  by  admixture 
with  a  mouthful  of  water,  tea,  or  other  liquid. 


4  PHYSIOLOGY  OF  ALIMENTATION. 

The  act  of  swallowing  is  usually  divided  into  three  parts 
corresponding  to  the  anatomical  regions  through  which  the 
food  has  to  pass,  namely,  the  mouth,  the  pharynx,  and  the 
oesophagus.  But  this  division,  it  will  be  seen,  is  a  purely 
arbitrary  one  and  therefore  had  best  not  be  made.  In  its 
passage  through  the  mouth  and  the  upper  portion  of  the 
pharynx  the  food  may  be  kept  under  the  control  of  the  will. 
After  the  food  has  come  into  the  grasp  of  the  involuntary 
muscle  fibres  of  the  oesophagus  its  movement  can  no  longer 
be  controlled  voluntarily.  Under  ordinary  circumstances, 
however,  with  the  exception  of  the  voluntary  formation  of 
the  bolus,  the  entire  act  is  involuntary,  and  is  essentially 
reflex  in  character. 

The  best  experimental  observations  that  we  have  on  the  act 
of  deglutition  are  those  of  Kronecker  and  Meltzer,1  and 
those  of  Cannon  and  Moser.2  Although  the  experimental 
methods  adopted  by  these  investigators  are  radically  different, 
their  results  agree  in  the  main  very  well. 

Preparatory  to  the  act  of  deglutition  the  material  to  be 
swallowed  is  collected  into  a  bolus  through  the  combined 
movements  of  the  cheeks,  teeth,  and  tongue.  The  bolus 
rests  for  a  moment  on  the  dorsum  of  the  tongue.  According 
to  Kronecker  and  Meltzer  the  chief  factor  concerned  in 
forcing  food  through  the  pharynx  and  oesophagus  is  the  quick 
and  powerful  contraction  of  the  mylo-hyoid  muscles,  aided 
by  the  simultaneous  contraction  of  the  hyoglossi  muscles. 
The  contraction  of  these  sets  of  muscles  puts  the  bolus  of 
food  as  it  rests  on  the  dorsum  of  the  tongue  under  high 
pressure  and  shoots  it  in  the  direction  of  the  least  resistance 
through  the  pharynx  and  oesophagus.  By  the  contraction 
of  these  muscles  the  epiglottis  is  also  closed  over  the  tracheal 


1  Kronecker  and  Meltzer:  Archiv  fur  Physiologie,  1880,  p.  446; 
ibid.,  1883,  Suppl.  BJ.,  p.  337,  351.  Meltzer:  Journal  of  Experi- 
mental Medicine,  1897,  II,  p.  457. 

2  Cannon  and  Moser:  American  Journal  of  Fhysiology,  1898,  I,  p. 

435. 


MECHANICAL  PHENOMENA. 

opening.  Kronf.ckkr  and  Meltzkr  believe  that  the  food 
passes  in  a  spurt  from  the  beginning  of  the  pharynx  clear 
through  the  oesophagus  to  the  cardiac  orifice  of  the  stomach. 
The  contraction  of  the  constrictors  of  the  pharynx  und  the 
peristaltic  movements  of  the  oesophagus,  they  believe,  follow 
this  act  and  serve  to  remove  any  fragments  which  may  have 
adhered  to  the  oesophagus.  This  description  we  shall  see 
holds  only  for  liquids,  and  not  for  more  solid  foods.  They 
also  believe  that,  in  most  individuals  at  least,  the  food 
does  not  immediately  enter  the  stomach  but  is  stopped  at 
the  lower  end  of  the  oesophagus  by  a  contraction  of  the 
circular  muscle  fibres  of  the  cardia,  and  is  only  slowly  forced 
into  the  stomach  by  the  aftercoming  peristaltic  wave.  The 
experiments  of  Cannon  and  Moser  do  not  support  this  view. 

Cannon  and  Moser  studied  the  act  of  deglutition  in  various 
animals,  including  man,  by  following  the  passage  of  liquids, 
solids,  and  semi-solids  mixed  with  bismuth  subnitrate  from 
the  mouth  to  the  stomach  by  means  of  the  a;-ra3Ts.  The 
bismuth  subnitrate  renders  the  swallowed  mass  opaque  to  the 
x-rays,  and  as  this  method  necessitates  neither  anaesthetics, 
operative  procedures,  nor  recording  instruments  it  is  freer 
from  objection  than  some  of  the  older  means  employed  in  the 
study  of  deglutition.  According  to  these  authors  the  move- 
ment of  food  through  the  oesophagus  differs  markedly  not 
only  in  different  animals  but  also  in  the  same  animal  with 
food  of  different  consistencies.  In  fowls,  for  example,  the 
rate  of  movement  through  the  oesophagus  is  always  slow,  and 
no  matter  what  the  consistency,  it  is  carried  from  the  pharynx 
into  the  stomach  by  peristaltic  waves.  A  squirt-like  move- 
ment when  liquids  are  swallowed  is  impossible  in  these  ani- 
mals, as  the  parts  forming  the  mouth  are  too  rigid.  In  order 
to  get  the  swallowed  mass  within  the  grasp  of  the  oesophageal 
musculature  the  head  is  raised  to  aid  the  weak  propulsive 
powers  of  the  mouth  as  largely  as  possible  by  gravity. 

In  the  cat  also  the  food  is  moved  through  the  oesophagus 
by  peristalsis,  but  somewhat  more  rapidly  than  in  the  case 


6  PHYSIOLOGY  OF  ALIMENTATION. 

of  fowls.  It  requires  nine  to  twelve  seconds  for  a  bolus  of 
solid  food  to  reach  the  stomach,  and  a  somewhat  shorter  time 
for  liquids  to  make  the  same  journey.  The  reason  for  this 
difference  lies  in  the  fact  that  liquids  move  somewhat  more 
rapidly  in  the  upper  portion  of  the  oesophagus  than  do  semi- 
solids. In  the  lower  portion  of  the  oesophagus  the  rate  for 
both  kinds  of  food  is  approximately  the  same.  For  all  kinds 
of  food  the  rate  of  movement  in  the  upper  half  of  the  oesoph- 
agus is  somewhat  greater  than  in  the  lower  half. 

In  the  dog  swallowing  approximates  the  same  act  in  the 
human  being.  The  total  time  for  the  descent  of  a  bolus  of 
food  in  this  animal  is  from  four  to  five  seconds.  In  the  upper 
portion  of  the  oesophagus  the  movement  is  always  more  rapid 
than  in  the  lower,  and  when  the  swallowed  mass  is  liquid 
this  rapid  movement  continues  deeper  into  the  oesophagus 
than  when  it  is  solid  or  semi-solid.  No  distinct  pause  occurs 
when  the  bolus  changes  from  its  rapid  rate  to  the  slower  one. 

In  man  liquids  are  propelled  deep  into  the  oesophagus  at  a 
rate  of  several  feet  a  second  by  the  sudden  and  sharp  con- 
traction of  the  mylo-hyoid  muscles.  This  confirms  the  obser- 
vations of  Kronecker  and  Meltzer.  According  to  Cannon 
and  Moser,  however,  solids  and  semi-solids  are  not  swallowed 
in  the  same  way.  From  studies  on  a  seven-year-old  girl 
who  was  given  gelatine  capsules  filled  with  bismuth  sub- 
nitrate,  or  bread-and-milk  mush  mixed  with  the  same  salt, 
they  conclude  that  the  movement  of  food  of  these  con- 
sistencies through  the  oesophagus  is  always  accomplished  by. 
peristalsis.  Nor  does  the  food  in  its  passage  through  the 
oesophagus  stop  before  it  enters  the  stomach,  which  Kro- 
necker and  Meltzer  believed  to  be  the  case.  Only  the  rate 
of  progressive  movement  changes  from  a  more  rapid  one  in 
the  upper  oesophagus  to  a  slower  one  lower  down. 

4.  The  Movements  of  the  Stomach. — The  movements  of 
the  various  portions  of  the  alimentary  tract  from  the  oesoph- 
agus to  the  rectum  have  been  the  object  of  research  of 
many    investigators    for    many    years.     The    pages  of  this 


MECHANICAL   PHENOMENA.  7 

volume  do  not  allow  even  an  outline  <>f  the  various  views 
which  have  been  held  from  time  to  time.  Many  of  these 
we  now  know  to  he  entirely  false,  others  in  part,  often  in 
large  part,  correct. 

Within  recent  years  a  number  of  papers  have  appeared 
on  the  movements  of  the  gastro-intestinal  tract  which  have 
given  us  a  clearer  insight  into  this  problem.  Foremost 
among  these  newer  researches  stand  the  observations  of 
Cannon  in  this  country  and  Houx  and  Bathazard  in 
Trance.  The  observations  of  these  men  are  free  from  many 
of  the  objections  which  may  be  lodged  against  the  older 
studies  of  the  subject. 

Experiments  in  mammalian  physiology  must  of  necessity 
be  so  often  carried  on  under  anaesthetics  or  the  disturbing 
influence  of  operative  procedures  that  when  these  factors 
affect  the  physiological  process  which  is  being  investigated 
results  are  obtained  which  if  not  wrong  are  at  least  con- 
fusing. It  is  to  the  disturbing  influences  of  the  methods 
used  in  the  investigation  of  the  movements  of  the  gastro- 
intestinal tract  by  the  older  observers  that  some  of  their 
confusing  results  are  to  be  attributed,  and  it  is  but  natural 
that  the  introduction  of  experiments  in  which  all  operative 
interference,  anaesthetics,  etc.,  are  shut  out  should  yield 
more  trustworthy  results  than  our  older  ones;  while  they 
indicate  to  us  at  the  same  time  what  is  right  and  what  is 
wrong  in  our  older  conceptions. 

Cannon  and  Roux  and  Bathazard  used  the  x-ray  in 
their  study  of  the  movements  of  the  alimentary  tract.  This 
does  away  with  the  necessity  of  surgical  operations  in  order 
to  obtain  a  view  of  the  intestines,  and  at  the  same  time 
prevents  the  exposure  of  the  abdominal  contents  to  the  cold 
of  the  air,  to  evaporation,  etc.,  all  of  them  important  factors 
in  modifying  the  normal  activity  of  the  hollow  viscera. 
In  order  to  render  the  food  visible  within  the  alimentary 
tract,  bismuth  subnitrate  was  mixed  with  it.  Since  this 
substance  is  opaque  to  the  x-rays,  the  food  may  readily  be 


8  PHYSIOLOGY  OF  ALIMENTATION. 

followed  in  its  passage  through  the  alimentary  tract  by  plac- 
ing a  fluoroscopic  screen  over  the  animal. 

The  only  possible  sources  of  error  which  might  have  crept 
into  these  observations  of  Cannon  and  Roux  and  Batha- 
zard  are  therefore  those  connected  with  tvinp-  thp  animal  dowji 

while   making   nbsprva.t.irm.si  fl.nrl   t,hp  fpprjinp;  OT"  bismuth  ^gub- 

nitrate  with  the  food.  That  the  first  plays  no  role  in  care- 
fully conducted  experiments  is  indicated  by  the  fact  that 
observations  carried  out  on  sleeping  animals  agree  per- 
fectly with  those  carried  out  on  waking  ones.  So  far  as  the 
bismuth  subnitrate  is  concerned  the  objection  will  be  made 
that  it  inhibits  the  intestinal  movements,  as  it  is  used  for 
this  purpose  in  the  treatment  of  diarrhoeas.  But  care  must 
be  taken  in  applying  what  holds  for  an  inflamed  gastro- 
intestinal tract  to  a  healthy  one,  in  which  the  action  of  the 
bismuth  subnitrate  is  at  its  worst  but  slight. 

We  shall  follow  first  of  all  Cannon's  1  description  of  the 
movements  of  the  stomach  in  the  cat. 

The  form  of  the  active  stomach  a  few  minutes  after  a 
meal  of  15  grams  of  milk  and  bread  mixed  with  3  to  5  grams 
of  bismuth  subnitrate  is  shown  in  Fig.  1.  For  convenience 
in  description  the  stomach  may  be  divided  into  two  parts. 
The  larger  cardiac  part  lies  to  the  animal's  left  of  the  line 
through  vox.  The  smaller  pyloric  part  lies  to  the  right  of 
this  line  and  consists  of  two  subdivisions,  the  antrum  to 
the  animal's  right  of  a  line  passing  through  yz,  and  a  pre- 
antral  part  to  the  left  of  this  line  and  extending  to  the  line 


Gannon:  American  Journal  of  Physiology,  1898, 1,  p.  359.  See  also 
Roux  and  Bathazard:  Comptes  rendus  de  la  soc.  de  biologie,  1897, 
IV,  p.  785;  Archives  de  Physiologie,  1898,  X,  p.  85.  A  review  of  the 
older  literature  on  the  movements  of  the  stomach  may  be  found  in 
Cannon's  paper.  See  also  Beaumont:  Physiology  of  Digestion,  Bur- 
lington, 1847, p.  104;  Hofmeister  and  Echtjtz:  Archiv  f.  exper.  Patho- 
logie  und  Pharmakologie ,  1885,  XX,  p.  1;  Rossbach:  Deutsches 
Archiv  f.  klin.  Medizin,  1890,  XL VI,  p.  296;  Hirsch:  Centralblatt  f. 
klin.  Medizin,  1892,  XIII,  p.  994. 


MECHANICAL  PHENOMENA.  9 

through  vox.     The  antrum  is  closed  by  the  pyloric  sphincter 
at  p. 

The  wall  of  the  stomach  consists  of  three  layers  of  smooth 
muscle  fibres,  an  outer  longitudinal,  a  middle  circular,  and 
an  inner  oblique  coat.  Smooth  muscle  is  characterized 
physiologically  by  its  power  of  slow  rhythmic  contraction 
and  relaxation  and  its  power  of  prolonged  contraction  (tonic- 
ity). The  role  that  these  characteristics  play  in  determining 
the  normal   movements  of   the  stomach   can  be   best  appre- 


Rife'lu 


(Copied  from  Cannon:  American  Journal  of  Physiology,  1898,1,  p.  360.) 

ciated  by  a  study  of  the  accompanying  figures,  which  indi- 
cate the  changes  that  occur  in  the  shape  of  the  stomach 
after  an  ordinary  meal  (Fig.  2). 

Within  five  minutes  after  a  meal  of  bread  a  slight  annular 
constriction  appears  near  the  duodenal  end  of  the  antrum 
and  moves  peristaltically  towards  the  pylorus.  This  is 
followed  by  several  other  waves  of  similar  character.  Two 
or  three  minutes  after  the  first  movement  is  seen,  very  slight 
constrictions  appear  near  the  middle  of  the  stomach  (the 
preantral  part)  and  becoming  deeper  move  slowly  toward 
the  pylorus.  As  digestion  goes  on  the  antrum  becomes 
somewhat  elongated  and  the  constrictions  somewhat  deeper, 
but  never  until  the  stomach  is  nearly  empty  do  they  divide 
the  cavity  entirely.  The  waves  recur  at  intervals  of  almost 
exactly  ten  seconds  and  take  about  thirty-six  seconds  to 
pass  from  the  middle  of  the  stomach  to  the  pylorus.  When 
one  wave  is  just  beginning  several  others  are  therefore  already 


10  PHYSIOLOGY  OF  ALIMENTATION. 


Fig.  2. 
(Copied  from  Cannon:  American  Journal  of  Physiology,  1898, 1, p.  370.) 


MECHANICAL  PHENOMENA. 


11 


Or       ? 


Fig.  2 — Continued. 


12  PHYSIOLOGY  OF  ALIMENTATION. 

running  before  it  as  indicated  in  Fig.  2  (11.30-1.30).  Between 
the  rings  of  constriction  the  stomach  is  bulged  out.  Cannon 
has  calculated  the  number  of  waves  which  pass  over  the_ 
ptnmach   d.11r^nff  «■  sinfrlp  digestive  period  lasting  apprpxi- 

rnat.ply  aftvftn  hours  an  2fiOD. 

The  food  slowly  passes  out  of  the  stomach  into  the  duode- 
num. The  exact  manner  in  which  this  happens  has,  however, 
been  variously  described  by  different  authors.  Those  who 
with  Hirsch  saw  the  food  pass  from  the  stomach  into  the 
duodenum  at  intervals  are  probably  correct.  In  cats,  Cannon 
found  that  no  food  appeared  in  the  duodenum  until  the  con- 
strictions had  been  passing  over  the  antrum  for  ten  or  fifteen 
minutes.  When  the  food  did  appear  it  was  squirted  through 
the  pylorus  for  some  distance  along  the  intestine.  Every 
constriction  wave  does  not  force  food  through  the  pylorus. 
Several  waves  usually  pass  over  the  antrum  before  one  is  ef- 
fective in  this  particular.  At  times  two  or  three  succeeding 
waves  may  each  force  food  through  the  pylorus,  but  usually 
it  remains  closed  for  some  time  after  it  has  allowed  one  con- 
striction wave  to  pass  food  into  the  duodenum.  The  cause 
of  this  opening  and  closing  of  the  pylorus  will  be  discussed 
further  on. 

When  a  hard  bit  of  food  reaches  the  pylorus  the  sphincter 
closes  tightly  and  remains  closed  longer  than  when  the  food 
is  soft.  This  can  be  shown  experimentally  by  feeding  along 
with  an  ordinary  meal  pellets  of  bismuth  subnitrate  made  up 
with  starch  paste.  These  can  be  readily  recognized  as 
darker  spots  in  the  general  shadow  cast  by  the  gastric  contents 
upon  the  fluoroscopic  screen.  When  such  pellets  are  given 
with  the  regular  meal  the  stomach  is  emptied  more  slowly 
than  when  the  food  has  a  uniform  consistency. 

We  have  thus  far  spoken  only  of  the  movements  of  the 
pyloric  half  of  the  stomach.  How  does  the  cardiac  half 
behave?  For  many  years  this  has  been  looked  upon  as  a 
sort  of  reservoir  for  the  swallowed  food,  but  it  has  always 
been    considered    purely   passive,     Cannon's   experiments 


MECHANICAL  PHENOMENA.  13 

show  that  it  is  indeed  a  reservoir,  but  a  most   active  one. 

The  changes  which  (he  cardiac  half  of  the  stomach  suffers 
during  an  ordinary  digestive  period  is  shown  in  the  drawings, 
which  were  made  by  tracing  the  outlines  of  the  stomach  on 
tissue-paper  laid  over  the  abdomen  of  the  cat  at  various 
times  after  feeding. 

By  comparing  .the  figures  it  can  be  seen  that  as  digestion 
goes  on  the  antrum  seems  to  elongate  and  acquire  a  greater 
capacity,  and  that  the  constrictions  make  deeper  indenta- 
tions into  it  (Fig.  2,  11.00-1.30).  When  the  fundus  has  lost 
most  of  its  contents  the  longitudinal  and  circular  fibres  of 
the  antrum  contract  and  make  it  shorter  and  of  less  capacity 
once  more.  As  compared  with  the  changes  in  the  form  of 
the  rest  of  the  stomach  those  in  the  antrum  are  slight. 

The  first  region  to  decrease  markedly  in  size  is  the  pre- 
antral  part,  at  the  beginning  of  which  the  peristaltic  waves 
commence.  These  gradually  force  some  of  the  stomach 
contents  in  this  region  into  the  antrum,  so  that  the  pre- 
antral  part  little  by  little  begins  to  assume  a  tubular  form 
in  consequence  of  the  sustained  (tonic)  contraction  of  the 
muscle  fibres  of  this  region  (Fig.  2,  1.30-2.30).  At  one 
end  of  this  tube  we  have  the  rounded  fundus,  at  the  other 
the  actively  contracting  antrum.  Shallow  constrictions  may 
pass  along  the  tubular  portion. 

The  muscle  fibres  (longitudinal,  circular,  and  oblique)  found 
in  the  fundus  gradually  contract  upon  the  spherical  mass  of 
food  found  here  and  slowly  force  it  into  the  tubular  portion. 
The  size  of  the  fundus  thus  gradually  diminishes,  until  the 
shadow  cast  by  this  portion  of  the  stomach  entirely  dis- 
appears (Fig.  2,  5.00-5.30).  The  tubular  portion  of  the 
stomach  forces  the  food  on  into  the  antrum,  until  finally, 
when  the  fundus  is  empty,  the  last  remnants  of  food  are 
squeezed  out  of  the  tubular  portion  into  the  antrum. 

We  see  from  the  above  that  the  time  which  the  food  spends 
in  the  stomach  is  considerably  longer  than  is  commonly 
supposed.     In  the  illustrations  it  can  be  seen  that   all  the 


14  PHYSIOLOGY  OF   ALIMENTATION. 

food  had  not  passed  out  of  the  stomach  seven  hours  after 
feeding.  The  same  holds  true  for  the  human  being,  though 
absolute  quantity  of  food  and  its  chemical  and  physical 
character  have  much  to  do  with  its  passage  into  the 
duodenum.  A  large  meal  would,  other  things  being  equal, 
take  longer  to  leave  the  stomach  than  a  smaller  one.  It 
was  pointed  out  above  that  coarse  particles  of  food  delay 
the  opening  of  the  pylorus,  and  so  keep  a  meal  in  the  stomach 
a  correspondingly  longer  time.  One  of  the  pernicious  results 
of  incomplete  mastication  of  the  food  may  well  be  traced 
to  this  fact.  We  shall  see  below  how  the  opening  and  closing 
of  the  pyloric  sphincter  is  affected  still  more  powerfully  by 
the  chemical  constitution  of  the  food. 

We  can  readily  appreciate  the  value  of  an  organ  which, 
as  the  stomach,  retains  the  swallowed  food  and  only  little 
by  little  passes  it  on  into  the  intestinal  canal  beyond.  In 
this  way  the  food  does  not  become  heaped  up  in  any  sec- 
tion of  the  small  or  large  bowel  until  the  rectum  is  reached, 
and  greater  chance  for  the  chemical  elaboration  of  the  vari- 
ous foodstuffs  and  for  their  absorption  is  obtained  in  con- 
sequence. 

Having  considered  the  movements  of  the  stomach-wall, 
we  must  discuss  briefly  the  movements  of  the  food  within 
the  stomach.  The  older  observations  regarding  this  point 
are  very  contradictory. 

As  was  shown  above,  waves  pass  rhythmically  over  the 
antrum.  The  food  squeezed  forward  by  an  undulation 
may  have  one  of  two  things  happen  to  it.  If  the  pylorus 
is  open  the  wave  serves  to  push  the  food  on  into  the  duo- 
denum. We  saw  above,  however,  that  by  no  means  every 
wave  is  effective  in  this  direction.  For  the  majority  of 
waves  it  might  almost  be  said  the  pylorus  remains  closed. 
Under  these  circumstances  the  food  is  forced  into  the  blind, 
pouch-like  extremity  of  the  antrum.  When  this  occurs  a 
part  at  least  of  the  food  which  is  being  pressed  upon  is  forced 
backward  through  the  constriction  towards  the  cardiac  end 


MECHAMCAL  PHENOM  EN  A.  15 

of  the  stomach.  Cannon  was  able  to  show  that  the  food 
actually  moves  in  this  way  by  mixing  with  it   starch-paste 

pellets  of  bismuth  subnitrate,  the  excursions  of  which  could 
readily  be  followed  among  the  other  food.  When  the  pylorus 
is  closed  the  food  is  squirted  back  through  the  oncoming 
constriction  with  considerable  force.  A  subsequent  wave 
then  carries  the  food  toward  the  pylorus  once  more.  In  this 
way  the  food  is  brought  in  contact  with  the  mucous  mem- 
brane of  the  stomach  over  and  over  again,  and  thus  besides 
undergoing  a  certain  degree  of  mechanical  division  becomes 
thoroughly  mixed  with  the  gastric  juice.  Interestingly 
enough,  it  is  from  this  more  active  pyloric  half  of  the  stomach 
that  the  largest  secretion  of  gastric  juice  occurs. 

While  digestion  is  going  on  and  all  the  time  that  the 
antrum  is  most  busily  engaged  in  kneading  and  rekneading 
the  food  in  this  portion  of  the  stomach  the  food  in  the  car- 
diac half  shows  no  sign  of  movement.  Bismuth-subnitrate 
balls  contained  in  the  food  which  lies  in  the  fundus  keep 
their  relative  positions  until  the  fundus  begins  to  contract 
and  then  move  slowly  forward  toward  the  antrum.  This 
observation  should  settle  for  all  time  the  question  of  salivary 
digestion  in  the  stomach.  As  is  well  known l  the  amylase 
and  maltase  of  the  saliva  do  not  act  upon  starch  or  maltose 
respectively  wThen  even  a  small  percent  of  any  acid  is  pres- 
ent. Careful  examination  of  the  fundus  contents  after  a 
starchy  meal  by  Cannon  and  Day2  have  shown  that  no_ 
inconsiderable  amount  of  salivary  digestion  occurs  in  the 
stomach.  Herein  we  find  another  fact  indicative  of  the 
importance  of  thorough  mastication  and  insalivation  of  the 
food  before  it  is  swallowed.  Food  thus  prepared  can  undergo 
salivary  digestion  in  the  cardiac  half  of  the  stomach,  perhaps 
even  for  hours  before  it  is  brought  to  a  standstill  by  becom- 
ing mixed  with  the  hydrochloric  acid  of  the  gastric  secre- 
tion. 


'  Seep.  103. 

2  Cannon  and  Day:   American  Journal  of  Physiology 


16  PHYSIOLOGY  OF  ALIMENTATION. 

5.  The  Passage  of  Different  Foodstuffs  from  the  Stomach. 
The  Opening    and  Closing    of   the   Pyloric    Sphincter. — It 

is  the  function  of  the  pylorus,  through  the  contraction 
of  the  muscular  fibres  contained  in  it,  to  keep  the  gas- 
tric contents  from  being  forced  out  of  the  stomach  whi'/e 
subjected  to  the  churning  movements  of  this  organ.  At 
certain  times,  however,  the  pylorus  relaxes  and  allows  a 
part  of  the  gastric  contents  to  pass  through.  Some  of  the 
older  observers  believed  that  the  pylorus  was  contracted 
during  the  entire  digestive  period  and  that  only  when  the 
food  had  been  thoroughly  mixed  with  the  gastric  juice  did 
it  relax  and  allow  the  stomach  to  empty  itself  entirely  and 
at  once.  We  know  now,  from  the  findings  of  Ewald,  Boas,1 
and  Penzoldt2  with  the  stomach- tube,  and  the  more  per- 
fect experiments  of  Cannon  3  with  the  x-rays,  that  the 
stomach  empties  itself  little  by  little  through  periodic  open- 
ings and  closings  of  the  pylorus.  As  has  been  shown  above, 
the  peristaltic  waves  of  the  stomach  pass  continuously 
under  normal  conditions  from  the  middle  of  the  stomach 
to  the  pylorus.  As  long  as  the  pylorus  is  closed  these  waves 
serve  only  to  churn  the  food  and  mix  it  thoroughly  with 
the  gastric  secretion.  When  the  pylorus  relaxes,  how- 
ever, these  same  waves  serve  to  push  the  gastric  contents 
into  the  duodenum.  What  now  determines  this  periodic 
opening  and  closing  of  the  sphincter? 

Hirsch  4  observed  in  1893  that  when  an  acid  is  intro- 
duced into  the  duodenum  through  a  duodenal  fistula  the 
escape  of  the  gastric  contents  from  the  stomach  is  delayed 
for  some  time.  Serdjukow  5  confirmed  this  finding  in  1S99. 
About  the  time  of  Hirsch's  observations,  Penzoldt  found 


1  Ewald  and  Boas:    Virchow's  Archiv,  1885,  CI,  p.  364. 

2  Penzoldt.   Deut.  Arch.  f.  klin.  Med.,  1893,  LI,  p.  545. 

3  Cannon:  Am.  Jour,  of  Physiol.,  1898, 1,  p.  368. 

4  Hirsch:  Centralblatt  fur  klin.  Medizin,  1893,  XIV,  p.  73. 

5  Serdjukow:    Russian  dissertation  reviewed  in  Hermann's  Jahres- 
bericht  ub.  d.  Fortschritte  d.  Physiologic,  1899,  VIII,  p.  214. 


MECHANICAL  PHENOMENA.  17 

that  those  foods  which  delay  the  appearance  of  free  hydro- 
chloric acid  in  the  stomach  remain  longest  in  this  organ. 
More  recently  Cannon  x  has  reinvestigated  (his  subject, 
confirmed  the  findings  of  Penzoldt,  and  outlined  a  theorj 
of  the  action  of  the  pylorus  which  agrees  with  experimental 
and  clinical  facts  as  we  know  them  to-day. 

Cannon  investigated  the  rate  at  which  different  food- 
stuffs leave  the  stomach  to  enter  the  small  intestine.  As 
examples  of  a  nearly  pure  protein  diet,  boiled  beef  free  from 
fat,  boiled  whitefish  or  the  white  meat  of  fowls  was  used. 
Beef-suet,  mutton-fat,  or  pork-fat  served  as  nearly  pure 
fats,  while  starch  paste,  rice,  and  potatoes  were  taken  as 
examples  of  a  carbohydrate  diet.  Definite  amounts  of  the 
various  foods  mixed  with  bismuth  subnitrate  were  fed 
to  full-grown  cats  which  had  been  without  food  for  twenty- 
four  hours  previously,  and  by  means  of  the  .r-ray  the 
rapidity  was  noted  with  which  the  various  foodstuffs  escape 
into  the  intestine.  The  time  at  which  the  food  begins  to 
move  into  the  duodenum  can  be  accurately  determined  in 
this  way,  and  by  measuring  the  aggregate  length  of  the 
shadows  in  the  small  intestine  at  half-hour  or  hourly  in- 
tervals the  relative  amounts  of  food  in  the  intestine  from 
time  to  time  can  be  fairly  well  gauged. 

In  the  following  curves  (Fig.  3)  constructed  from  Can- 
non's figures  are  indicated  the  different  velocities  with 
which  protein,  fat,  and  carbohydrate  leave  the  stomach. 
It  will  be  seen  that  the  fats  and  carbohydrates  begin  to 
move  out  of  the  stomach  soon  after  ingestion,  the  carbo- 
hydrates leaving  very  rapidly,  while  the  fats  leave  only 
slowly.  The  curve  representing  the  carbohydrates  (curve  C) 
rises  rapidly  to  a  maximum  which  is  reached  at  the  end 
of  the  second  hour,  to  fall  more  slowly  after  this  point  is 
passed.  The  curve  for  fats  (curve  .1)  both  rises  and  falls 
slowly,  does  not  reach  its  maximum  until  the  third  hour, 

1  Cannon:  Journal  <»t  the   \m.  Med.  Assoc,  L905,  XI. IV.  p.  15. 


18 


PHYSIOLOGY  OF  ALIMENTATION. 


and  at  no  time  even  approaches  the  maximum  points  reached 
by  the  carbohydrates  or  proteins.  The  protein  curve 
(curve  B)  possesses  the  greatest  interest.  Not  only  do 
the  proteins  begin  to  pass  out  of  the  stomach  much  later 
than  either  fats  or  carbohydrates  (often  none  of  the  gas- 


2  3  4 

Hours  after  Feeding 

Fig.  3. 

A  =  fat;    J3=protein;    B'  =  acidulated  protein;    C  =  carbohydrate; 
C"  =  alkalinized  carbohydrate. 

trie  contents  leave  the  stomach  before  the  end  of  the  first 
hour  after  a  protein  meal),  but  their  maximum  velocity  is 
not  attained  until  the  end  of  the  fourth  hour.  It  will  be 
noticed  that  these  findings  harmonize  with  those  of  Penzoldt. 
What    now   determines   that    carbohydrates    upon   which 


Mechanical  phenomena.  10 

the  gastric  juice  has  iki  effect  should  leave  the  stomach 
quickly  while  proteins  which  are  digested  in  the  stomach 
should  remain  here  a  long  time?  The  observation  of  Pen- 
zoldt  that  those  foods  which  combine  with  the  hydrochloric 

acid  of  the  stomach  are  t  he  last,  to  leave  this  viscus  lias 
been  pointed  out  above.  It  is  the  presence  of  free  hydro- 
chloric acid  in  the  stomach  and  near  the  pylorus  thai  deter- 
mines the  relaxation  of  the  sphincter  and  explains  why 
different  foodstuffs  enter  the  small  intestine  at  different  rates. 
As  will  be  shown  later  1  an  abundance  of  gastric  juice  is 
poured  out  on  both  a  protein  and  a  carbohydrate  diet.  A 
diet  consisting  chiefly  of  fat  causes  the  secretion  of  much 
less  juice.  Now  since  carbohydrates  cause  a  great  secretion 
of  gastric  juice  but  do  not  unite  chemically  with  the  acid, 
free  hydrochloric  acid  accumulates  almost  at  once  in  the 
stomach.  Proteins,  on  the  other  hand,  unite  with  the  acid 
of  the  gastric  juice  and  hence  prevent  the  accumulation  of 
free  acid  for  a  considerable  length  of  time.  Finally,  fat 
calls  forth  only  a  slight  secretion  of  gastric  juice,  but  that 
which  is  produced  soon  accumulates  in  the  stomach,  as  it 
does  not  unite  with  the  fat.  These  facts  explain  the  dif- 
ferent rates  at  which  the  various  foods  pass  out  of  the 
stomach. 

The  idea  that  it  is  the  presence  of  free  hydrochloric  acid 
in  the  stomach  which  determines  the  relaxation  of  the 
sphincter  can  be  still  further  tested.  If  a  carbohydrate 
meal  is  mixed  with  an  alkaline  fluid  it  delays  the  appear- 
ance of  free  hydrochloric  acid  in  the  stomach.  Such  a  meal 
we  find  also  leaves  the  stomach  much  later  than  the  pure 
carbohydrate.  This  is  indicated  in  curve  C"  in  Fig.  3.  It 
will  be  seen  that  the  curve  for  alkalinized  carbohydrate 
tends  to  approximate  that  for  ordinary  protein. 

It  is  possible  to  try  the  converse  of  this  experiment  by 
feeding    acidulated    protein   from    which  any  excess   of   acid 

1  See  (  li;ipt  r  XT,  Part  2. 


20  PHYSIOLOGY  OF  ALIMENTATION. 

has  been  removed  and  noting  the  rate  at  which  this  food  is 
discharged  from  the  stomach.  When  acidulated  protein  is 
fed,  the  hydrochloric  acid  of  the  gastric  juice  is  allowed  to 
accumulate  from  the  beginning.  As  is  indicated  in  curve 
B'  in  Fig.  3,  corresponding  to  this  fact,  we  find  that  acidu- 
lated protein  leaves  the  stomach  as  rapidly  as  pure  carbo- 
hydrate,— in  fact,  the  two  curves  almost  coincide. 

It  might  be  thought  at  first  that  the  addition  of  an  acid 
to  a  pure  carbohydrate  meal  would  hasten  its  discharge 
from  the  stomach.  Experiment  shows  that  this  is  not  the 
case,  for  a  curve  showing  the  velocity  with  which  a  meal  of 
crackers  mixed  with  0.4  percent  hydrochloric  acid  leaves 
the  stomach  practically  coincides  with  that  furnished 
by  an  equally  large  meal  consisting  of  crackers  and  water 
only.  How  is  this  fact  to  be  explained?  We  find  an  answer 
in  the  observations  of  Hirsch  and  Serdjukow  quoted  above, 
who  found  that  the  presence  of  an  acid  in  the  duodenum 
causes  the  discharge  of  food  from  the  stomach  to  be  delayed. 
Whether  this  was  due  to  a  contraction  of  the  pyloric  sphincter 
or  to  a  cessation  of  the  movements  of  the  stomach  could, 
however,  not  be  determined  in  their  experiments.  We 
know  now  from  Cannon's  researches  that  the  peristaltic 
movements  of  the  stomach  are  continuous,  so  that  Hirsch's 
and  Serdjukow's  findings  must  be  explained  through  a 
contraction  of  the  pyloric  sphincter. 

We  see  therefore  that  two  factors  are  concerned  in  the 
opening  and  closing  of  thepylorus.  The  pylorus  opens  when- 
ever free  hydrochloric  acid  of  sufficient  concentration  is 
present  in  the  stomach.  The  opening  of  the  pylorus  allows 
the  escape  of  a  part  of  the  acid  stomach  contents  into  the 
duodenum.  As  soon  as  the  acid  comes  in  contact  with  this 
portion  of  the  intestinal  tract,  however,  the  pylorus  is  made 
to  close  and  remains  closed  until  the  acid  in  the  duodenum 
is  neutralized  through  the  flow  of  the  pancreatic  juice  and  bile 
into  this  portion  of  the  gut.  As  will  be  shown  later,  the  pres- 
ence of  acid  in  the  duodenum  is  a  determining  condition 


MECHANICAL  PHENOMENA.  21 

for  the  flow  of  juice  from  the  pancreas.1  As  the  acid  in  the 
duodenum  becomes  neutralized  the  stimulus  to  the  closure 
of  the  pylorus  is  weakened  until  the  acid  in  the  stomach 
once  more  opens  the  sphincter.  Another  portion  of  food 
in  consequence  escape?  from  the  stomach,  the  pylorus  closes 
once  more,  and  the  cycle  is  repeated. 

Automatically,  therefore,  carbohydrates  which  are  not 
acted  upon  by  the  gas!ric  juice  leave  the  stomach  soon  after 
ingestion  and  quickly,  while  proteins  which  are  digested 
in  this  viscus  are  retailed  and  discharged  only  slowly.  The 
intestine  is  spared  in  ;his  way  large  doses  of  acid  stomach 
contents  which  unless  neutralized  interfere  so  markedly 
with  the  digestive  functions  of  the  intestine. 

The  behavior  of  fat  differs  a  little  from  that  of  the  carbo- 
hydrates and  proteins.  The  immediate  but  slower  discharge 
from  the  stomach  is  explained  in  part  by  the  small  amount 
of  gastric  juice  which  is  poured  out  upon  fat.  The  gastric 
peristalsis  after  a  meal  consisting  mainly  of  fat  is  also  not 
as  vigorous  as  that  found  after  a  meal  of  protein  or  carbo- 
hydrate. Moreover,  as  soon  as  fats  enter  the  duodenum  the}7 
cause  the  same  closure  of  the  pylorus  which  is  caused  by 
acids.2  In  this  way  the  fats  are  kept  for  a  long  time  in  the 
stomach. 

1  See  Chapter  XII,  Partt  2,  4  and  5. 

2  Lintwarew;  Biochemisches  Centralblatt,  1903,  I,  p.  96,  quoted 
by  Cannon. 


CHAPTER  II. 

THE  MECHANICAL  PHENOMENA  OF  ALIMENTATION 

(Continued). 

6.  The  Movements  of  the  Small  Intestine. — A  review  of 
the  literature  on  the  movements  of  the  intestine,  both  large 
and  small,  may  be  found  in  the  articles  of  Grutzner  x  and 
Cannon  2  and  in  the  section  on  the  intestine  by  Starling  3  in 
Schaefer's  Text-book  of  Physiology.  The  following  para- 
graphs sum  up  Cannon's  conclusions  on  the  movements  of 
the  intestine  as  studied  by  the  already  outlined  method  of 
rr-ray  examination  of  the  alimentary  tract  after  a  meal  mixed 
with  bismuth  subnitrate.  Cats  fed  on  canned  salmon  or 
bread-and-milk  mush  were  used  for  experimental  study. 

It  is  best  to  begin  a  description  of  the  normal  movements 
of  the  small  intestine  by  referring  to  Fig.  4,  in  which  is  shown 
the  appearance  of  the  food  in  the  intestine  of  a  cat  five  and 
three-quarter  hours  after  a  meal  of  canned  salmon.  The 
animal  is  lying  upon  her  back.  In  the  middle  of  the  plate 
in  dim  outline  is  seen  the  spinal  cord  with  the  pelvis  below. 
On  the  right  side  above  is  the  pyloric  extremity  of  the  stom- 
ach, and  below  it  in  dark  shadow  several  intestinal  loops 
lying  over  each  other.  In  lighter  outline  and  occupying  the 
entire  abdominal  cavity  are  other  loops  also  filled  with  food. 
The  small  dark  shadow  on  the  left  is  the  caecum. 

1  Grutzner:  Pfliiger's  Archiv,  1898,  LXXI,  p.  515. 
?  Cannon:  American  Journal  of  Physiology,  1902,  VI,  p.  251. 
3  Stabling:    Schaefer's  Text-book  of  Physiology,  Edinburgh  and 
London,  1900,  II,  p.  330. 

22 


]■"!. 


(From  an  .r-ray  photograph  kindly  sent  me  |>y  1  )r.  C.vxxox.) 


23 


MECHANICAL  PHENOMENA.  2"> 

When  sufficient  time  has  elapsed  so  that  the  food  has  been 
distributed  through  the  intestine  as  indicated  in  Fig.  4,  and 
the  animal  is  exposed  to  the  x-rays,  it  is  found  that  mosl 
of  the  loops  are  in  a  state  of  perfect  rest.  This  is  due  only 
to  the  excited  state  of  the  animal.  After  a  time,  if  the 
cat  is  allowed  to  remain  quiet,  the  intestinal  movements 
begin.  Two  chief  kinds  of  intestinal  movement  may  then 
be  recognized:  first,  movements  of  rhythmic  segmentation, 
and  secondly,  peristaltic  movements.  By  far  the  more  com- 
mon of  these  two  movements  is  the  first  named.  Sway- 
ing movements,  such  as  have  been  described  by  the  older 
observers,  are  also  seen  at  times. 

The  character  of  the  rhythmic  segmentation  can  be  best  un- 
derstood by  reference  to  Fig.  5.  The  movements  consist 
essentially  in  the  sudden  division  of  one  of  the  long  narrow 
strings  of  food  lying  in  one  of  the  loops  shown  in  Fig.  4 
into  a  large  number  of  segments  of  nearly  equal  size.  These 
segments  are  then  suddenly  divided  and  neighboring  halves 
unite  to  form  new  segments,  after  which  the  process  is  re- 
peated. This  division  and  redivision  of  the  food  follow  each 
other  many  times  in  succession.  In  line  1  of  Fig.  5  is  shown 
the  food  as  it  lies  in  a  loop  of  intestine  in  the  quiescent  state. 
Suddenly  as  the  movements  of  rhythmic  segmentation  evidence 
themselves,  this  string  of  food  is  divided  into  a  large  number 
of  nearly  equal  segments  as  indicated  in  line  2.  A  moment 
later  each  of  these  segments  is  divided  in  two  pieces,  and 
the  neighboring  pieces  unite  to  form  a  new  segment.  Thus 
a  and  b  of  line  2  unite  to  form  the  segment  c  of  line  3.  When 
this  division  occurs  the  end  segments  A  and  B  remain  small. 
But  the  next  segmentation  which  divides  the  segments  of 
line  3  restores  the  old  order  of  things,  for  the  end  pieces  re- 
unite with  the  halves  of  their  adjoining  segments  to  form 
the  new  segments  indicated  in  line  4.  This  series  of  seg- 
ments it  will  be  seen  corresponds  to  the  series  shown  in 
line  2.  The  process  of  division  and  redivision  of  the  food 
continues  under  ordinary  circumstances  uninterruptedly  for 


26  PHYSIOLOGY  OF  ALIMENTATION. 

more  than  half  an  hour,  during  all  of  which  time  the  form 
scarcely  changes  its  position  in  the  abdomen.  In  one 
instance  the  segmentation  was  seen  to  continue  with  only 
three  short  periods  of  inactivity  for  two  hours  and  twenty 
minutes. 

The  above  description  holds  for  the  usual  movements  of 
the  small  intestine,  and  when  the  food  is  not  too  thickly 
crowded  in  that  region  of  the  gut.  When  too  large  an 
amount  of  food  is  present  in  any  given  portion  of  the  in- 


i  OCDOCDOcS A 

600000^ 


Fig.  5. 

(Copied  from  Cannon:  American  Journal  of  Physiology,  1902, 

VI,  p.  256.) 

testine  the  constrictions  may  not  completely  divide  the 
string  of  food,  but  only  in  part.  This  condition  of  affairs 
is  illustrated  in  line  1  of  Fig.  6. 

Furthermore,  the  constrictions  do  not  always  take  place 
in  the  middle  of  a  segment,  but  more  toward  one  side  of  it, 
as  indicated  by  the  dotted  divisions  in  line  1  of  Fig.  6.  In 
this  way  one-third  of  each  segment  may  be  pinched  off  at 
each  division,  and  only  every  third  segmentation  restores 
the  original  order  of  the  series.  Thus,  in  Fig.  6,  the  first 
division  occurs  along  the  dotted  line  a  in  each  segment. 
This  brings  about  the  state  of  affairs  shown  in  line  2.  In 
this  series  the  fragment  of  food  at  the  extreme  right  of  the 
string  consists  of  one-third  of  an  original  segment,  while  that 
at  the  extreme  left  consists  of  about  two-thirds  of  a  segment. 
The  next  division  which  takes  place  along  the  dotted 
line  b  brings  about  the  condition  of  affairs  indicated  in  line 


MECHANIC  A L  PHENOMENA. 


27 


3,  in  which  two-thirds  of  an  original  segment  is  present  on 
the  right-hand  end  of  the  string  of  food  and  one-third  on 
the  left  hand.  Not  until  the  third  division  occurs  along  the 
dotted  line  c  is  the  original  arrangement  of  the  segments 
restored. 

The  rapidity  with  which  the  segmenting  movements  occur 
is  exceedingly  interesting.  If  each  segmentation,  that  is  to 
say,  if  every  change  from  one  line  to  another  in  the  diagrams, 
is  counted,  it  is  found  that  from  twenty-eight  to  thirty  occur 
each  minute.  If  the  string  of  food  is  thin,  only  rarely  does 
the  rate  fall  as  low  as  twenty-three  in  the  same  unit  of  time. 
When  much  food  is  present  in  a  given  segment  of  intestine, 


J-  *  *       w      wc    w 


Fig.  6. 

(Copied  from  Cannon:  American  Journal  of  Physiology,  1902, 

VI,  p.  258.) 

as  indicated  in  Fig.  6,  the  number  may  fall  as  low  as  eighteen 
to  twenty-one  per  minute. 

Cannon  has  calculated  that  a  slender  string  of  food  may 
commonly  undergo  division  into  small  segments  more  than 
a  thousand  times  without  changing  its  position  in  the  intes- 
tine. The  admirable  purpose  which  this  serves  in  thoroughly 
mixing  the  food  with  the  digestive  juices  and  bringing  it  in 
contact  with  the  absorbing  mucous  lining  of  the  intestine 
will  at  once  become  apparent.  Moreover,  as  Mall  l  has 
pointed  out  these  repeated  rhythmical  contractions  greatly 

1  Mall:  Johns  Hopkins  Hospital  Reports,  I,  p.  37. 


28  PHYSIOLOGY  OF  ALIMENTATION. 

aid  in  the  propulsion  of  the  blood  into  the  portal  circulation 
and  the  movement  of  the  lymph  through  the  lacteals.  As 
absorption  and  secretion  by  the  intestinal  mucosa  are  both 
markedly  influenced  by  the  character  of  the  blood  which 
flows  through  this  tissue,  it  can  at  once  be  seen  how  impor- 
tant these  rhythmical  contractions  are. 

We  turn  now  to  a  consideration  of  the  peristaltic  move- 
ments in  the  small  intestine.  Peristalsis  shows  itself  in  two 
forms,  first  as  a  slow  advancement  of  the  food  for  a  short 
distance  in  a  coil,  and  secondly,  as  a  rapid  movement  which 
sweeps  the  food  through  several  loops  of  the  gut.  The  latter 
is  frequently  seen  under  normal  conditions  when  the  food  is 
carried  forward  from  the  duodenum.  It  is  produced  arti- 
ficially by  injecting  soap-suds  into  the  rectum. 

When  a  mass  of  food  has  been  subjected  to  the  already 
described  segmenting  movements  for  a  time,  the  latter  may 
suddenly  cease  and  the  separate  segments  begin  to  move  slowly 
forward,  each  segment  following  closely  upon  its  predecessor. 
After  moving  forward  in  this  way  for  a  few  centimeters  the 
anterior  segment  comes  to  a  stop,  and  the 
succeeding  ones  are  swept  into  it,  until 
a      6  the  food  lies  stretched  along  the  intestine 

(3XZ)  ^     as   a    solid,  resting  string  of  food. 

Sometimes  a  single  large  mass  of  food, 

^^2>  cQ  3     sucn  as  *s   indicated   in    Fig.  7,  is  pushed 

forward.       A  long  string   of    food   is    first 

—*(^    >    ^     crowded  together  into  a  more  rounded  mass, 

such  as  is  shown  in  line  1.     Suddenly  this 

,n  ■  lG.'  '  ^  mass  is  indented  in  the  middle  and  assumes 
(Copied  irom  Can-  . 

non:    American  in   consequence    the   shape   shown   in   line 

Journal  of  Phy-  2.      A   second   division  now  occurs  in  the 

siology,  1902,  VI    posterior  portion  a  which  may  cause  the 

p.  260.)  severed    part    to    fly    backward    for    some 

distance  in  the   intestine,  when  a   succeeding   contraction 

again  unites  all  the  pieces  into  a  rounded  mass  and  pushes  the 

whole  slightly  forward.    This  is  shown  in  line  4  of  Fig.  7. 


MECHANICAL  PHENOMENA.  29 

7.  The  Movements  of  the  Large  Intestine. — As  will  be 
described  in  greater  detail  later  the  food  passes  from  the 
small  intestine  through  the  ileocecal  valve  into  the  ascend- 
ing colon,  and  under  normal  circumstances  this  valve  is 
competent  to  the  food  which  has  passed  through  it.  From 
differences  in  physiological  function  we  must  distinguish 
between  the  first  portion  of  the  large  gut  which  is  com- 
posed of  the  ascending  and  transverse  colon,  and  the  second 
portion  which  is  made  up  of  the  descending  colon.  Not 
only  do  the  intestinal  movements  differ  in  these  two  por- 
tions of  the  large  bowel,  but  also  their  contents.  For  while 
palpation  shows  that  the  food  in  the  caecum,  ascending  and 
transverse  colons  is  soft,  so  that  the  walls  of  the  gut  can 
readily  be  approximated,  it  is  found  that  the  contents  of 
the  descending  colon,  sigmoid  flexure,  and  rectum  are  made 
up  of  hard,  incompressible  lumps. 

By  far  the  commonest  normal  movement  of  the  ascending 
and  transverse  portions  of  the  large  bowel  is  that  of  anti- 
peristalsis,  that  is  to  say,  the  peristaltic  waves  visible  in 
this  portion  of  the  intestinal  tract  occur  in  a  direction  toward 
the  stomach  and  away  from  the  rectum.  The  first  food 
which  enters  the  colon  from  the  small  intestine  is  carried 
by  these  anti-peristaltic  waves  into  the  caecum.  The  con- 
tents of  the  colon  are  not,  therefore,  as  is  generally  believed, 
carried  forward  toward  the  rectum  by  a  slow  peristalsis, 
but  are  instead  pushed  backward  a  large  number  of  times 
by  these  anti-peristaltic  waves.  These  anti-peristaltic  waves 
begin  at  the  most  advanced  portion  of  the  food,  or,  if  con- 
siderable is  present,  at  the  splenic  flexure,  from  which  they 
sweep  backward  toward  the  caecum.  The  average  dura- 
tion of  a  period  of  anti-peristalsis  is  four  to  five  minutes, 
and  the  periods  recur  every  ten  to  twenty  minutes.  Between 
the  periods  the  colon  is  quiet. 

As  the  ileocaecal  valve  is  competent  under  normal  circum- 
stances, the  anti-peristaltic  waves  do  not  force  the  food 
out  of   the  large  intestine   back   into   the  small   intestine. 


30  PHYSIOLOGY  OF  ALIMENTATION. 

The  constrictions  as  they  pass  over  the  colon  therefore 
force  the  food  into  a  blind  pouch.  As  the  food  does  not 
burst  through  the  caecum  while  subjected  to  the  ever-in- 
creasing pressure  of  the  contractile  ring  it  can  only  escape 
through  the  advancing  ring.  We  have  already  become 
familiar  with  this  phenomenon  in  the  stomach  when  the 
peristaltic  waves  pass  over  it  against  a  closed  pylorus. 
In  the  colon,  therefore,  we  have  the  food  again  subjected 
to  a  thorough  mixing,  and  another  opportunity  is  pre- 
sented for  absorption. 

The  movements  characteristic  of  the  descending  colon  are 
a  series  of  tonic  constrictions  which  pass  downwards  toward 
the  rectum.  As  the  food  accumulates  in  the  ascending 
colon  it  is  at  first  confined  to  the  region  of  anti-peristalsis. 
As  more  food  enters  the  ascending  colon  the  contents  of 
the  large  bowel  are  forced  over  more  and  more  into  the 
transverse  and  descending  portions.  After  a  time,  as  the 
food  approximates  the  splenic  flexure  a  deep  constriction 
appears  which  pinches  off  a  globular  mass  from  the  main 
body  of  the  food  as  indicated  in  A,  Fig.  8.  This  constric- 
tion persists,  in  other  words,  is 
a  tonic  one.  The  globular  mass 
now  moves  slowly  forward  toward 
the  rectum,  and  as  it  passes 
onward  down  the  descending 
FlG   g#  colon    new  constrictions    appear 

(Copied  from  Cannon:  Amer-  which  again  pinch  off  globular 
ican  Journal  of  Physiology,  masses  from  the  advancing  food 
1902,  VI,  p.  268.)  column  in  the  transverse  colon. 

This  is  shown  in  Fig.  9.  These  rings  slowly  move  down 
the  descending  colon,  pushing  the  rounded  masses  of  food 
before  them  until  they  reach  the  sigmoid  flexure  and  rectum. 
Even  during  the  short  passage  from  the  splenic  flexure  into 
the  rectum  some  absorption  occurs,  for  the  food  masses 
which  are  pinched  off  in  the  transverse  colon  are  much 
softer  than  the  dry  faeces  which  collect  in  the  rectum. 


(From  an  x-ray  photograph  kindly  senl  me  by  Dr.  Cannon.) 


31 


Fig.  10. 
(From  an  x-ray  photograph  kindly  sent  me  by  Dr.  Cannon.) 


33 


MECHANICAL  PHENOMENA.  35 

8.  Defaecation. — The  act  of  defalcation  is  in  pari  an  invol- 
untary, and  in  part  a  voluntary,  process.  The  first  part  of 
the  act  is  involuntary  and  may  be  described  as  follows-  In 
the  cat  the  entire  large  bowel  seems  to  swing  around  so  thai 
the  ascending  colon  is  raised  to  occupy  in  part  the  posit  inn 
formerly  held  by  the  transverse,  and  this 
the  position  originally  occupied  by  the 
descending  colon.  This  is  apparent  when 
Fig.  11,  which  shows  the  beginning  of  the 
act  of  defalcation,  is  compared  with  Fig.  10, 
which  shows  the  position  of  the  large  in- 
testine under  ordinary  circumstances.  The 
tonic  constrictions  pictured  in  Fig.  10  dis- 
appear at  the  same  time,  and  their  place  is 
taken  by  a  single  broad  contraction  of  the 
circular  muscle  which  tapers  off  the  in- 
testinal contents  on  both  sides  of  it.  In 
this  way  a  faecal  mass  lying  low  in  the 
descending  colon  is   pinched   off    from    the  F|G    ^ 

intestinal  contents  higher  up.  The  broad  (Copied  from  Can- 
contraction  now  passes  slowly  downward  non.  American 
and,  aided  by  the  voluntary  contraction  of      Journal  oi  Phy 

the  abdominal  muscles    and  the   voluntary      ^ogy,vn.      • 

VI    p.  2/0.) 
relaxation  of  the  anal  sphincter,  which  con- 
stitute the  second   part  of  the  act   of   defaecation,   pushes 
the  faecal  mass  out  of  the  canal. 

When  the  external  act  of  defaecation  has  been  thus  accom- 
plished, the  colon  with  its  remaining  contents  returns  to 
nearly  its  former  position  (Fig.  12).  From  the  time  that  the 
colon  begins  to  change  its  position  until  it  returns  to  it  once 
more  takes  about  20  minutes.  When  the  original  position 
has  been  reassumed  the  slowly  moving  contractions  begin 
again,  and  the  contents  of  the  large  intestine  which  were  not 
lost  in  the  act  of  defaecation  are  slowly  spread  into  the 
emptied  portion  of  the  descending  colon. 

Just  how  the  intestinal  contents  got  from  the  region  of  the 


36  PHYSIOLOGY  OF  ALIMENTATION. 

anti-peristaltic  waves  in  the  colon  to  the  region  of  the  slowly 
advancing  rings  is  not  yet  entirely  understood.  In  part  the 
later  portions  of  the  food  push  that  which  has  gone  before 
ahead  of  it.  But  the  ascending  and  transverse  portions  of  the 
colon  can  get  rid  of  most  of  their  contents  even  in  starvation, 
though  they  are,  perhaps,  never  entirely  emptied  even  under 
these  conditions.  Apparently  strong  tonic  peristaltic  waves 
at  times  pass  over  the  ascending  and  transverse  colon  and 
force  the  contents  of  these  portions  of  the  large  bowel  into  the 
region  of  the  descending  colon,  where  peristaltic  waves  are  the 
rule. 

9.  The  Movement  of  Food  through  the  Alimentary  Tract 
as  a  Whole. — The  process  of  mastication  takes  a  varying 
length  of  time,  depending  upon  the  nature  of  the  food  and  to 
a  large  extent  upon  the  individual.  Dry  food  takes  longest 
to  become  mixed  with  saliva  sufficiently  to  allow  of  its  being 
swallowed,  while  liquids  are  at  once  passed  backward  toward 
the  oesophagus.  The  entire  length  of  time  required  for  the 
food  to  fall  into  the  stomach  after  mastication  is  completed 
varies  with  different  animals,  the  extremes  being  represented 
by  four  and  twelve  seconds.  In  man  from  four  to  seven 
seconds  are  required  from  the  initiation  of  the  act  of  deglu- 
tition to  the  time  the  food  falls  into  the  stomach. 

The  food  remains  in  the  stomach  a  variable  number  of 
hours,  depending  upon  the  quantity  and  the  quality  of  the 
food  ingested.  Other  things  being  equal,  a  small  amount  of 
food  will  escape  into  the  small  intestine  in  shorter  time  than 
a  larger  amount.  The  time  that  food  remains  in  the  stomach 
is  probably  greater  than  is  generally  believed  to  be  the  case. 
An  average  meal  does  not  ordinarily  leave  the  stomach  en- 
tirely in  less  than  six  hours.  The  quality  of  the  food  plays 
an  important  role  by  determining  the  frequency  with  which 
the  pyloric  sphincter  relaxes  and  allows  the  food  to  be  forced 
onward  into  the  duodenum  by  the  contractile  waves  which 
pass  over  the  antrum.  As  was  shown  above,  not  every  wave 
forces  food  out  of  the  stomach. 


Fig.  l 


(From  an  x-ray  photograph  kindly  sent  me  by  Dr.  Cannon.) 


MECHANICAL  PHENOMENA.  39 

When  the  pylorus  relaxes  the  food  is  squirted  for  a  con- 
siderable distance  along  the  duodenum  (Fig.  13),  where  it  lies 
quietly  until  added  to  by  further  contributions  from  the 
stomach.  In  this  way  a  long  thin  string  of  food  is  formed. 
During  all  this  time  the  pancreatic  and  bile  ducts  pour  the 
secretions  from  their  respective  organs  into  the  food.  All  at 
once  the  string  of  food  breaks  up  into  several  segments,  and 
the  process  of  rhythmic  segmenta- 
tion already  described  above  is  0 
started.     After  this  has  continued  for           o 

some    minutes    the    segments    unite 

o 
into    a    single     large    mass,    or   into  0      Fig.    13. 

groups,    and   slowly  pass    along   the  (Copied    from    Cannon: 

gut.     Near  the  pylorus  the  peristalsis  Ame"can    Jo"rnal    of 

■w,i             ,            •      +u  Physiology,    1902,    VI, 

is  more  rapid  than  lower  down  in  the  lco  . 

1  p.  2b2.) 

small    intestine.      "The  masses  once 

started  go  flying  along,  turning  curves,  whisking  hither  and 
thither  in  the  loops,  moving  swiftly  and  continuously  for- 
ward." L  After  passing  forward  in  this  way  for  some  dis- 
tance the  food  is  collected  again  into  thick  and  long  strings 
and  the  process  of  segmentation  repeated.  The  strings 
of  food  may  remain  lying  quietly  in  a  loop  of  intestine 
for  an  hour  or  more.  During  the  first  stages  of  digestion  the 
food  lies  chiefly  on  the  right  side  of  the  abdomen,  during  the 
later  stages  chiefly  on  the  left.  By  these  combined  move- 
ments of  segmentation  and  peristaltic  advance,  both  of  which 
are  repeated  from  time  to  time,  the  food  is  finally  brought  to 
the  ileocecal  valve. 

The  time  elapsing  before  the  food  enters  the  duodenum 
from  the  stomach  varies,  as  already  pointed  out,  with 
the  nature  of  the  food.  In  general  it  may  be  said  that  no 
food  enters  the  small  intestine  until  one  or  one  and  a  half 
hours  after  eating.  Five  to  six  hours  elapse  after  eating 
before  food  begins  to  appear  in  the  large  intestine,  so  that  it 

1  Cannon:  American  Journal  of  Physiology,  PKI'i,  VI,  p.  2t>.'J. 


40  PHYSIOLOGY  OF  ALIMENTATION. 

is  evident  that  approximately  five  hours  are  required  by  the 
food  to  traverse  the  small  intestine. 

The  food  about  to  pass  into  the  large  intestine  is  directed 
toward  the  latter  from  some  distance  back  in  the  small  gut  (see 
Fig.  8,  B).  From  here  it  moves  slowly  along  the  ileum  and  is 
pushed  through  the  valve  into  the  colon  to  fall  into  the 
caecum.  This  passage  of  food  through  the  ileocecal  valve 
seems  to  act  as  a  stimulus  which  excites  the  colon  to  activity. 
As  the  food  approaches  the  ileocaecal  valve  the  large  intestine 
is  quiet  and  relaxed.  As  soon,  however,  as  the  food  has 
entered  it  a  strong  contraction  takes  place  along  the  ceecum 
and  lower  portion  of  the  ascending  colon,  which  is  followed 
immediately  by  the  anti-peristaltic  waves  which  have  already 
been  described  and  which  continue  running  for  two  or  three 
minutes. 

Under  ordinary  circumstances  the  succeeding  masses  of 
food  force  the  older  portions  onward  through  the  large 
bowel,  but  even  in  starvation  most  of  the  contents  of  the 
large  bowel  are  gotten  rid  of.  But  a  complete  emptying 
of  the  large  intestine  seems  never  to  occur.  The  time 
which  the  food  spends  in  the  large  intestine  varies  of  course 
with  the  intervals  elapsing  between  succeeding  defsecations. 
The  time  which  the  intestinal  contents  spend  in  the  ascend- 
ing and  transverse  portions  of  the  large  bowel  is  certainly  to 
be  measured  in  hours.  During  all  this  time  absorption  is 
actively  going  on.  As  the  food  passes  into  the  descending 
colon,  sigmoid  flexure,  and  rectum  this  absorption  is  probably 
considerably  diminished. 

The  voluntary  part  of  the  act  of  defalcation  is  preceded 
by  an  involuntary  act  of  preparation  which  takes  an  hour 
or  more.  This  is  the  time  required  for  the  intestinal  con- 
tents to  pass  from  above  into  that  portion  of  the  lower 
bowel  which  has  been  emptied  by  the  last  act  of  defsecation. 
The  voluntary  part  of  the  act  of  defsecation  takes  only  a 
few  seconds,  depending  upon  the  amount  and  consistency 
of  the  defalcated  mass. 


MECHANICAL  PHENOMENA.  41 

10.  The  Nervous  Control  of  the  Alimentary  Tract. — We 
are  still  far  from  a  correct  understanding  of  the  relation  of 
the  nervous  system  to  the  movements  of  the  various  parts 
of  the  alimentary  tract.  The  experimental  results  obtained 
by  the  score  of  investigators  who  have  busied  themselves 
with  this  problem  do  anything  but  harmonize,  a  fact  not 
strange  when  the  difficulties  standing  in  the  way  of  the 
solution  of  the  problem  are  considered.  Narcotics,  operative 
procedures,  etc.,  all  so  markedly  influence  the  movements 
of  the  alimentary  tract  that  when  these  constitute  the  neces- 
sary means  which  must  be  utilized  in  a  study  of  the  problem 
uniform  results  can  scarcely  be  expected.  The  following 
paragraphs  follow  in  the  main  Starling's1  recent  review  of 
the  subject. 

The  act  of  deglutition  is  only  in  part  voluntary,  and  may 
as  a  whole  be  considered  as  an  essentially  reflex  act.  The 
reflex  is  initiated  whenever  the  palatine  branches  of  the  tri- 
facial, the  glosso-pharyngeal,  and  superior  laryngeal  nerves 
are  stimulated  either  through  the  presence  of  food  or  saliva 
in  the  mouth  or  by  artificial  means  as  when  an  electrical 
stimulus  is  applied  to  the  central  end  of  the  divided  superior 
laryngeal  nerve.  The  afferent  nerves  pass  into  the  medulla, 
in  the  upper  portion  of  which  is  situated  a  "centre"  whose 
destruction  is  associated  with  impairment  or  total  loss  of  the 
power  to  swallow.  The  impulses  which  go  to  bring  about  a 
movement  of  the  muscles  concerned  in  the  act  of  swallowing 
leave  the  medulla  chiefly  by  way  of  the  trifacial,  facial, 
and  glosso-pharyngeal.  The  oesophagus  is  supplied  almost 
solely  by  the  vagus. 

The  oesophagus  has  the  power  of  spontaneous  peristaltic 
contractions ;  within  the  body,  however,  the  waves  which 
pass  over  the  oesophagus  in  the  ordinary  act  of  swallowing 
seem  to  be  intimately  connected  with  an  uninjured  nervous 
system.     Division  of   the   nerves  supplying   the   <vsophagus 

r 

1  Starling:  Ergebnlsse  der  Physiologic,  L902, 1,  2te  Abth.,  p.  446. 


42  PHYSIOLOGY  OF  ALIMENTATION. 

causes  a  stoppage  of  the  oesophageal  movements.  Simple 
ligature  of  the  oesophagus  without  injury  to  the  nerves  does 
not,  however,  keep  the  oesophageal  movements  from  passing 
over  the  entire  length  of  the  oesophagus.  A  piece  can  even 
be  cut  out  of  the  oesophagus  and  if  the  nervous  connections 
between  the  upper  and  lower  ends  have  not  been  injured  the 
swallowing  movements  inaugurated  in  the  upper  end  pass 
(by  way  of  the  nerves)  over  the  lower  end  also.  It  seems 
therefore  as  though  the  ordered  act  of  deglutition  which  is 
started  through  stimulation  of  certain  afferent  nerves  is 
dependent  in  the  last  analysis  upon  impulses  which  pass 
from  an  excited  "centre"  by  way  of  certain  efferent  nerves 
to  the  oesophagus,  one  segment  after  another  of  which  is 
thereby  made  to  contract. 

The  stomach  is  supplied  with  cranial  nerves  by  way  of  the 
two  vagi,  and  with  sympathetic  nerve  fibres  by  way  of  the 
splanchnics  and  the  solar  plexus.  The  vagi  contain  fibres 
which  not  only  bring  about  movements  in  the  stomach 
but  also  such  as  inhibit  movement.  Under  ordinary  circum- 
stances, more  especially  when  the  stomach  contains  food, 
stimulation  of  the  vagi  brings  about  a  contraction  of  the 
cardiac  end  of  the  stomach;  or  one  or  a  series  of  contractions 
arise  in  the  preantral  portion  of  the  stomach;  or,  finally, 
the  musculature  of  the  whole  stomach  may  go  into  a  state 
of  tonic  contraction  which  gradually  increases  and  then 
after  a  longer  or  shorter  period  of  sustained  contraction  as 
gradually  relaxes.  Under  certain  circumstances  stimulation 
of  the  vagi  may  have  an  opposite  effect.  Especially  after 
the  administration  of  pilocarpin  may  stimulation  be  followed 
by  muscular  relaxation.  The  sympathetic  nerves  supplying 
the  stomach  in  a  certain  sense  antagonize  the  action  of  the 
vagi.  If  the  splanchnic  nerves  are  stimulated  a  decrease  in 
the  tonus  of  the  gastric  musculature  as  well  as  a  decrease 
in  the  rhythmical  contractions  of  the  stomach  are  usually 
observed. 

In  addition  to  the  nerves  which  run  into  the  wall  of  the 


MECHANICAL  PHENOMENA.  43 

stomach,  there  exist  in  this  viscus  isolated  ganglion  cells 
and  nerve  fibres  from  the  plexus  of  AuERBACH  and  Meissner. 
These  local  nervous  elements  have  been  looked  upon  as 
causing  the  rhythmical  contractions  of  the  stomach,  but 
it  is  questionable  whether  the  unstriped  muscle  fibres  are 
not  themselves  responsible  for  this.  It  approximates  cor- 
rectness most  nearly,  no  doubt,  when  we  say  that  the  un- 
striped muscle  fibres  of  the  stomach  are  capable  of  the 
rhythmical  and  the  sustained  contractions  which  we  observe 
in  this  organ,  but  that  these  contractions  can  be  markedly 
influenced  through  the  nervous  system. 

In  addition  to  the  local  nerve-cells  and  plexuses,  and  the 
vagus  and  sympathetic  fibres  which  go  to  the  stomach, 
there  exist  in  the  spinal  cord  and  the  ganglia  at  the  base 
of  the  brain  so-called  "centres"  which  on  stimulation  lead 
to  muscular  contractions  or  relaxations  in  the  stomach,  but 
we  do  not  understand  how  these  different  elements  cooperate 
to  bring  about  the  ordered  movements  observed  in  this  viscus 
after  an  ordinary  meal,  or  the  disturbances  noted  in  certain 
pathological  states. 

The  small  intestine  is  supplied  by  branches  from  the  vagus 
nerves  and  from  the  sympathetic  system.  The  sympathetic 
fibres  come  to  the  intestine  in  part  from  the  solar  and  lum- 
bar plexuses,  in  part  by  way  of  the  splanchnics.  Stimu- 
lation of  the  vagus  brings  about  in  the  small  intestine  as 
in  the  stomach  motor  effects  which  may  evidence  them- 
selves in  rhythmical  contractions,  or  in  sustained  tonic  con- 
tractions. The  chief  effect  of  stimulation  of  the  sympa- 
thetic fibres  seems  to  be  that  of  inhibition.  As  was  first 
shown  by  Pfluger,  stimulation  of  the  splanchnics  leads  to 
cessation  of  movement  in  the  small  intestine.  From  Mall's  l 
careful  studies  it  is  known  that  an  anaemia  of  the  intestines 
causes  a  cessation  of  movement  in  them,  and  it  was  once 
thought  that  the  inhibition  of  movement  when  the  splanch- 

1  Mall:  Johns  Hopkins  Hospital  Reports,  1SD6,  I,  p.  37 


44  PHYSIOLOGY  OF  ALIMENTATION. 

nics  are  stimulated  was  secondary  to  the  anaemia  brought 
about  by  this  means.  But,  as  Bayliss  and  Starling  have 
shown,  such  inhibition  of  intestinal  movement  still  follows 
stimulation  of  the  splanchnics  in  freshly  killed  animals, 
in  other  words,  when  no  circulation  is  present.  Nothing 
definite  seems  to  be  known  regarding  the  role  of  the  plexuses 
of  Auerbach  and  Meissner  in  the  small  intestine.  Whether 
they  are,  in  the  last  analysis,  responsible  for  the  rhythmical 
contractions  of  the  jejunum  and  ileum  seems  questionable. 
This  power  probably  resides  in  the  musculature  itself. 

Stimulation  of  certain  regions  in  the  ganglia  at  the  base 
of  the  brain  and  certain  portions  of  the  spinal  cord  leads 
to  muscular  contractions  or  relaxations  in  the  small  in- 
testine by  way  of  the  vagus  and  sympathetic  nerves  supply- 
ing the  gut.  Some  connection  must  also  exist  between  the 
cerebrum  and  the  small  intestine,  for,  as  the  next  para- 
graphs show,  mental  states  may  cause  a  stoppage  of  all 
movement. 

It  has  long  been  a  recognized  clinical  fact  that  emo- 
tional states  such  as  fear,  anxiety,  sorrow,  etc.,  bring 
in  their  train  a  long  series  of  digestive  disturbances. 
The  physiological  pathology  of  these  disturbances  has  re- 
cently been  put  on  a  more  scientific  basis  by  a  series  of 
experimental  observations.  We  shall  later  become  ac- 
quainted with  facts  which  indicate  how  largely  certain  secre- 
tory phenomena  of  the  alimentary  tract  are  influenced  by 
psychic  states.  Here  mention  must  be  made  of  the  important 
relation  which  exists  between  mental  states  and  the  move- 
ments of  the  stomach  and  intestine.1 

Cannon  observed  in  his  studies  of  gastro-intestinal  move- 
ments that  female  cats  were  much  more  suitable  for 
experimental  purposes  than  males.  Even  though  treated 
exactly  alike  the  movements  which  appeared  almost  with- 

1  Cannon:  American  Journal  of  Physiology,  1898,  I,  p.  380;  ibid., 
1902,  VI,  p.  260. 


MECHANICAL  I'll  MOM  EN  A.  45 

out  exception  in  female  cats  were  almost  as  constantly 
wanting  in  male  cats.  Accompanying  this  was  always  a 
difference  in  the  behavior  of  the  cats  when  bound  into 
the  holder  for  observation.  While  the  females  would  lie 
quietly  and  purr,  the  males  would  fly  into  a  rage  and 
struggle  to  get  free.  The  following  observation  showed 
the  direct  connection  between  the  mental  state  and  the 
movements  of  the  gastrointestinal  tract.  A  male  cat 
which  had  been  fed  an  hour  and  a  half  previously  was  tied 
into  the  holder.  The  waves  were  passing  regularly  over 
the  stomach  at  the  rate  of  six  a  minute.  This  had  not 
lasted  long  when  the  cat  fell  into  a  rage  and  all  movement 
in  the  stomach  ceased  at  once. 

A  similar  relation  exists  between  the  mental  state  and 
the  movements  of  the  intestine.  This  is  not  surprising 
when  it  is  remembered  that  the  nerves  which  are  distributed 
to  these  two  portions  of  the  alimentary  tract  are  the  same. 
Whenever  a  cat  becomes  enraged  and  for  some  time  after 
it  is  again  pacified  the  movements  of  the  small  and  large 
intestine  cease  entirely.  Even  when  an  animal  is  only 
slightly  restless  in  the  holder  no  intestinal  movement  may 
be  apparent.  In  a  continuously 
fretful  cat  this  may  continue  for 
an  hour.  Between  the  periods  of 
excitement  the  intestinal  move- 
ments go  on  in  a  normal  manner. 
When  the  segmenting  movements 
in  the  small  intestine  cease,  the 
segments  of  food  coalesce  to  form 
a  single  long  string.     In  Fig.  14,  pIG<  ^4 

A,  is  shown  the  appearance  of  the  (Copied  from  Cannon:  Ameri- 
Iarge  intestine  when  the  anti-per-  can  Journal  of  Physiology, 
istaltic  waves  are  running  nor-  1902,  VI,  p.  275.) 
mally,  and  in  Fig.  14,  B,  how  the  same  region  of  the  intestine 
looks  when  the  anti-peristaltic  waves  are  inhibited  through 
excitement.     Interesting  is  the  fact  that  the  tonic  contrac- 


46  PHYSIOLOGY  OF  ALIMENTATION. 

tions  of  the  descending  colon  are  apparently  not  affected  by 
emotional  states,  for  they  do  not  relax  in  the  excitement 
which  causes  the  other  movements  to  cease. 

Inhibition  of  intestinal  movement  is  not  the  only  conse- 
quence of  excited  mental  states  Cannon  quotes  the  ex- 
periments of  Esselmont  and  Fubini  to  show  this.  Essel- 
mont  found  that  in  the  dog  signs  of  emotion  always  markedly 
increase  the  motor  activities  of  the  intestine,  though  only  for 
a  few  moments.  Fubini  noted  that  fear  brings  about  an 
increased  peristalsis. 

Finally,  the  fact  must  be  mentioned  that  all  movements  of 
the  intestines  go  on  during  sleep  in  the  same  way  as  in  the 
waking  hours. 

ii.  On  the  Action  of  Saline  Cathartics. — According  to  the 
generally  accepted  view  those  salts  which  are  classed  under 
the  head  of  the  saline  cathartics  in  the  works  on  pharmacology 
are  believed  to  exert  their  action  by  preventing  the  absorption 
of  water  from  the  intestinal  contents  as  the  latter  pass  through 
the  alimentary  tract.  In  this  way  it  is  believed  that  the 
ordinary  inspissation  into  the  compact  faeces  which  collect  in 
the  lower  bowel  is  prevented,  and  the  intestinal  tract  is  rid 
of  its  contents  in  the  form  of  very  soft  or  even  liquid  stools. 

It  seems  from  experiments  recently  carried  out  by  J.  B.  Mac- 
Callum  1  that  this  conception  can  no  longer  be  looked  upon  as 
the  correct  one.  MacCalltjm's  experiments  were  performed 
chiefly  on  rabbits,  but  dogs  and  cats  were  also  employed. 
The  salts  used  were  sodium  citrate,  sulphate,  tartrate,  oxalate, 
phosphate,  and  fluoride,  barium  chloride,  and  magnesium  sul- 
phate. These  experiments  have  shown  that  the  saline  purga- 
tives act  not  only  when  introduced  into  the  intestine,  but  also 
when  injected  subcutaneously  or  intravenously.  They  act 
most  powerfully,  however,  when  applied  directly  to  the  peri- 
toneal coat  of  the  intestine.     When  5  to  10  c.c.  of  a  one- 

1  MacCallum,  J.  B.:  American  Journal  of  Physiology,  1903,  X,  p. 
101;    Pfliiger's  Archiv,  1904,  CIV,  p.  421. 


MECHANICAL    PHENOMEN  I.  47 

eighth  molecular1  sodium  citrate  solution  are  injected  into 
the  lumen  of  the  intestine  of  a  rabbit,  increased  peristaltic 
movements  manifest  themselves  in  10  to  15  minutes.  About 
the  same  length  of  time  is  required  when  the  same  amount  of 
this  salt  solution  is  injected  subcutaneously.  When,  how- 
ever, only  1  to  2  c.c.  of  this  sodium  citrate  solution  are 
injected  intravenously,  a  striking  increase  in  intestinal  move- 
ments is  visible  in  one  to  two  minutes.  It  almost  seems  from 
these  experiments  that  the  saline  cathartics  must  be  ab- 
sorbed from  the  intestinal  tract  before  they  can  produce  their 
specific  effects.  A  reaction  in  the  form  of  a  local  constriction 
of  the  musculature  of  the  gut  is  obtained  almost  immediately 
after  painting  one  of  the  saline  cathartics  on  the  peritoneal 
coat  of  the  intestine. 

When  equimolecular  2  solutions  are  compared,  it  is  found 
that  by  far  the  most  powerful  of  the  cathartics  listed  above 
is  barium  chloride,  after  which  come  the  citrate,  fluoride, 
sulphate,  tartrate,  oxalate,  and  phosphate  of  sodium,  the 
intensity  of  the  action  of  which  decreases  approximately  in 
the  order  named.  The  intravenous  injection  of  a  solution  con- 
taining a  few  milligrams  of  the  dry  salt  is  sufficient  to  bring 
about  powerful  contractions  of  the  intestine.  The  power  of 
the  various  salts  to  produce  their  cathartic  action  was  deter- 
mined by  discovering  the  lowest  concentration  in  which  they 

1  That  is,  a  solution  of  sodium  citrate  made  by  dissolving  one  grain- 
molecule  of  the  dry  salt  in  enough  water  to  make  eight  litres.  A  gram- 
molecule  of  a  substance  is  the  molecular  weight  of  that  substance  (plus 
the  molecular  weight  of  its  water  of  crystallization,  if  it  has  any)  ex- 
pressed in  grams. 

2  That  is,  solutions  containing  the  same  number  of  gram-molecules  of 
the  various  salts  dissolved  in  the  unit  volume  of  the  solvent  (water  in 
this  case).  The  comparison  of  equal  percentage  solutions,  that  is 
solutions  containing  the  same  weight  of  the  salts  in  the  unit  volume  of 
Bolvent,  as  was  generally  done  by  the  older  observers,  leads  to  entirely 
erroneous  conceptions  of  the  relative  activity  of  the  dissolved  salts. 
It  would  be  well  if  all  workers  in  experimental  medicine  would  employ 
only  chemically  equivalent  solutions. 


48  PHYSIOLOGY  OF  ALIMENTATION. 

were  effective.  Magnesium  sulphate  is  about  as  active  a 
cathartic  as  sodium  sulphate,  but  it  is  by  no  means  as  harm- 
less as  the  latter.  MacCallum  found  that  magnesium  sul- 
phate was  often  fatal  in  doses  in  which  sodium  sulphate  is 
entirely  harmless.  This  statement  is  confirmed  by  some  of 
my  own  experiments  on  glycosuria,  in  which  it  was  found  that 
the  action  of  the  sulphate  of  sodium  is  less  harmful  than  that 
of  magnesium.  The  poisonous  action  is  apparently  deter- 
mined by  the  magnesium  constituent  in  the  latter  salt,  which 
has  a  powerful  effect  upon  the  heart.  A  practical  conclusion 
to  be  drawn  from  this  is  that  it  is  better  to  give  the  sodium 
salt  to  patients  than  the  magnesium  salt.  The  intensely 
poisonous  action  of  the  barium  chloride  should  also  put  a  ban 
upon  the  use  of  this  drug  in  medicine.  The  fluoride  and 
oxalate  also  have  specific  poisonous  properties  which  speak 
against  their  use  in  medicine,  especially  when  apparently 
harmless  salts  may  be  employed  with  just  as  good  results  if 
only  care  be  taken  to  use  the  right  amounts. 

The  purgative  action  of  the  saline  cathartics  depends  upon 
yet  another  factor  than  the  mere  increase  in  the  peristaltic 
movements  of  the  intestine,  namely,  an  increased  secretion 
of  fluid  into  the  intestine.  This  fact  was  observed  by  Gumi- 
lewski  *  and  Rohmann,2  and  is  confirmed  by  MacCalltjm's 
observations.  If  a  loop  of  intestine  is  tied  off  and  a  saline 
cathartic  is  injected  subcutaneously  or  intravenously,  or  is 
simply  painted  on  its  surface,  a  secretion  of  fluid  into  the 
loop  of  intestine  is  observed  in  addition  to  the  increased 
peristalsis. 

MacCallum  has  been  able  to  show  that  the  effect  of  the 
saline  cathartics  enumerated  above,  both  in  bringing  about 
an  increased  peristalsis  and  an  increased  secretion  of  fluid 
into  the  intestine,  can  be  counteracted  by  calcium  chloride, 
and  to  a  less  extent  by  strontium  and  magnesium  chloride. 
This  antagonism  between  sodium  and  calcium  salts  seems  to 

1  Gumilewski:  Pfliiger's  Archiv,  1886,  XXXIX,  p.  556, 

2  Rqhmann:  Pfliiger's  Archiv,  1887,  XLI,  p.  411, 


MECHAXICAL   PHENOMENA.  I!) 

exist  in  a  variety  of  physiological  reactions.  Ringer  ' 
called  attention  to  it  in  his  experiments  on  heart  muscle.  He 
found  that  the  contractions  of  ships  of  this  tissue,  which  are 
beating  rhythmically  in  sodium  chloride  solutions,  can  be 
inhibited  through  the  addition  of  a  calcium  salt  to  the  sodium 
chloride  solution.  The  experiments  of  Loeb,  who  has  elab- 
orated those  of  Ringer,  show  that  the  same  antagonism  exists 
in  the  case  of  voluntary  muscles  and  in  nerves.  Experiments 
of  other  investigators  are  at  hand  which  show  that  the  antag- 
onism between  calcium  and  sodium  salts  exists  in  the  involun- 
tary muscles  also,  but  these  experiments  are  not  entirely  free 
from  criticism,  for  no  special  means  were  taken  to  exclude  the 
effects  of  nerve  fibres  or  nerve-cells  present  in  the  preparations. 
Whether  the  increased  peristalsis  is  brought  about  directly 
through  the  action  of  the  saline  cathartics  upon  the  muscle- 
cells  themselves  or  only  indirectly  through  an  action  of  the 
salts  upon  the  nerve  plexuses  of  Auerbach  and  Meissner  has 
not  as  yet  been  definitely  settled.  It  is  certain  that  we  do 
not  need  to  go  beyond  the  wall  of  the  intestine  for  an  ex- 
planation of  the  action  of  these  drugs.  This  is  proven  by  the 
fact  that  pieces  of  gut  ligatured  and  cut  out  of  the  body  will 
show  their  characteristic  movements  when  immersed  in  solu- 
tions of  the  various  salines.  A  secretion  of  fluid  will  even  occur 
into  such  pieces  of  intestine.  This  indicates  that  the  ex- 
planation of  this  phenomenon  too  does  not  lie  beyond  the 
walls  of  the  alimentary  tract.  From  the  fact  that  very 
dilute  solutions  of  the  cathartics  produce  very  violent  and 
yet  entirely  local  contractions  in  the  intestine  when  painted 
upon  its  peritoneal  surface  it  seems  highly  probable  that  the 
increased  peristalsis  is  brought  about  through  a  direct  action 
upon  the  muscular  coat.  If  a  stimulation  of  nerves  lay  at 
the  foundation  of  the  increased  intestinal  movements  we 
would  expect  a  more  general  effect  from  the  local  applica- 
tions of  the  cathartic  salts. 

1  Ringeu:  Journal  of  Physiology,  18S4,  V,  p.  247. 


50  PHYSIOLOGY  OF  ALIMENTATION. 

iSo  far  as  the  quantitative  relation  is  concerned  which 
exists  between  the  dose  of  a  saline  purgative  sufficient  to 
affect  the  intestine  and  that  of  calcium  chloride  sufficient 
to  suppress  the  increased  peristalsis  and  intestinal  secretion 
brought  about  by  the  former,  it  may  be  said  that  a  chemically 
equivalent  amount  of  the  one  just  counteracts  the  other. 
If,  for  example,  a  certain  number  of  cubic  centimeters  of  a 
1/8  molecular  sodium  citrate  solution  are  injected  into  a 
rabbit  it  requires  an  equal  volume  of  a  1/8  molecular  calcium 
chloride  solution  to  counteract  the  effect  of  the  former.  This 
counteraction  takes  place  almost  immediately  if  the  calcium 
chloride  is  applied  to  the  peritoneal  coat  of  the  intestine. 
If  the  calcium  chloride  is  injected  intravenously  it  shows 
its  specific  effect  in  one  to  two  minutes,  but  it  takes  ten  to 
twenty  minutes  if  it  is  injected  subcutaneously  or  into  the 
lumen  of  the  intestine. 

MacCallum  is  inclined  to  explain  the  action  of  the  saline 
purgatives  through  their  power  of  diminishing  the  concen- 
tration of  the  free  calcium  ions  in  the  tissues  upon  which 
these  cathartics  act.  This  is  the  same  explanation  that  Loeb 
gives  of  the  twitchings  observed  by  him  when  voluntary 
muscles  are  immersed  in  these  same  salt  solutions.  The 
addition  of  a  calcium  salt  therefore  counteracts  the  effect  of 
the  saline  cathartics  by  restoring  the  concentration  of  the 
calcium  ions  and  so  bringing  the  intestine  back  to  its  original 
state.  It  must  be  remembered,  however,  that  barium 
chloride  is  the  most  powerful  of  all  the  salts  studied,  and 
yet  it  is  difficult  to  see  how  the  administration  of  such  traces 
of  this  substance  as  are  necessary  to  bring  about  a  violent 
catharsis  is  to  be  explained  by  its  effects  in  reducing  the 
concentration  of  the  free  calcium  ions.  Hofmeister's  belief 
that  Gatharsis  is  brought  about  through  the  coagulation  of 
certain  colloids  by  the  cathartic  salts  seems  less  open  to 
objection. 

The  movements  of  the  intestine,  as  a  whole,  under  the 
influence  of  saline  cathartics  have  not  yet  been  studied. 


MECTIA  NIC.  1  /.   PHENOM  EN  A .  51 

Whether  they  are  merely  exaggerated  forms  of  the  normal 
movements  or  differ  materially  from  the  latter  cannol  there- 
fore be  said  with  definiteness.  That  food  takes  a  very  much 
shorter  time  to  pass  the  length  of  the  alimentary  tract  under 
the  influence  of  saline  cathartics  is  a  well-known  clinical 
fact,  and  has  often  enough  been  proven  experimentally  by 
feeding  inert  substances  and  determining  the  time  required 
before  they  appear  in  the  freces.  The  greater  fluidity  of  the 
stools  we  must,  in  the  face  of  these  recent  experiments, 
attribute  to  the  increased  secretion  of  fluid  into  the  intestine 
and  not  to  a  decreased  absorption.  That  less  of  the  food 
is  absorbed  when  saline  cathartics  are  administered  shortly 
after  a  meal  is  in  part  dependent,  no  doubt,  upon  the  in- 
creased velocity  with  which  the  food  traverses  the  bowel. 
Less  time  is  allowed  in  consequence  for  the  products  of 
digestion  to  diffuse  through  the  intestinal  mucosa. 

The  cause  of  the  pain  (colic)  which  follows  the  ingestion 
of  the  saline  (and  other)  cathartics  is  also  not  entirely  under- 
stood. S.  J.  Meltzer  has  made  an  interesting  study  of  the 
subject.  This  author  holds  the  increased  force  of  the  con- 
tractions and  their  irregularity  responsible  for  the  pain 
in  all  forms  of  intestinal  colic. 

Further  work  with  the  rc-rays  would  teach  us  much  regard- 
ing the  movements  of  the  intestines  as  a  whole  under  ab- 
normal conditions.  That  after  the  administration  of  the 
saline  cathartics  it  is  probably  a  rapid  sweeping  peristalsis 
which  advances  the  food  through  several  coils  of  intestine, 
instead  of  the  normal  slow  peristalsis  which  moves  the  food 
onward  only  a  short  distance,  seems  very  probable  from  a 
statement  made  by  Cannon,1  who  observed  this  form  of 
movement  in  the  small  intestine  as  a  regular  consequence  of 
the  injection  of  soap-suds.  Many  of  the  soaps  resemble  in 
their  action  the  saline  cathartics. 

12.  The  Fate  of  Nutrient  Enemas. — While  certain  clinical 

1  Cannon:  American  Journal  of  Physiology,  190'-',  VI,  p.  200. 


52  PHYSIOLOGY  OF  ALIMENTATION. 

observers  have  been  unanimous  in  claiming  that  nutrient 
enemas  introduced  into  the  rectum  are  absorbed  and  utilized 
by  the  patient,  others  have  been  equally  certain  that  they 
are  of  little  or  no  value.  The  burden  of  evidence  is,  how- 
ever, in  favor  of  the  good  results  which  are  obtained  by 
this  method  of  artificial  feeding.  Lack  of  success  is  no 
doubt  in  large  measure  due  to  mistakes  made  in  the  com- 
position of  the  enemas  used,  for  the  absorption  of  many 
foods  can  occur  from  the  intestinal  tract  only  after  they 
have  been  acted  upon  by  the  digestive  juices. 

Leaving  aside  for  the  moment  the  chemical  aspects 
of  the  problem,  two  great  objections  have  been  brought 
against  the  efficacy  of  rectal  feeding.  The  first  of  these 
is  that  the  rectum  has  no  powers  of  absorption,  the  second 
that  the  food  does  not  pass  from  the  rectum  to  a  portion 
of  the  bowel,  where  it  can  be  absorbed.  It  must  be  con- 
fessed that  experimental  evidence  has  until  recently  been 
largely  in  favor  of  these  views.  With  scarcely  an  exception, 
investigators  have  come  to  the  conclusion  that  food  intro- 
duced into  the  rectum  does  not  move  far  away  from  it. 
Against  this  idea  has  stood  Grutzner,1  who  found  that  when 
certain  easily  recognizable  substances,  such  as  starch  grains, 
hair,  or  charcoal,  suspended  in  normal  salt  solution  are 
injected  into  the  rectum  they  are  carried  upward  through 
the  bowel  into  the  small  intestine,  even  as  far  as  the  stomach. 
More  recently  Cannon  2  has  brought  direct  proof  of  the  move- 
ment of  nutrient  enemas  from  the  rectum,  not  only  through 
the  large  intestine  but  even  into  the  small  intestine.  If  we 
admit,  therefore;  that  the  rectum  has  but  feeble  or  no  powers 
of  absorption,  we  can  no  longer  maintain  that  the  enemas 
are  not  moved  to  a  place  in  the  intestine  in  which  ab- 
sorption is  possible.  The  following  may  help  to  elucidate 
what  has  been  said: 


1  Grutzner:  Deutsche  med.  Wochenschrift,  1894,  XX,  p.  897. 

2  Cannon:  American  Journal  of  Physiology,  1902,  VI,  p.  272. 


MECHANICAL  PHENOMENA.  53 

In  order  to  ascertain  the  fate  of  enemas,  Cannon  intro- 
duced various  amounts  of  thick  and  thin  food  mixtures, 
holding  bismuth  subnitrate  powder  in  suspension,  into  the 
previously  cleaned  rectum  of  various  animals  and  observed 
what  happened  by  means  of  the  x-rays.  The  enemas  had 
the  following  composition: 

100  c.c.  milk, 
2  grams  starch, 

1  egg» 
15  grams  bismuth  subnitrate. 

To  make  the  enemas  thick  all  these  were  stirred  together 
and  boiled  to  a  soft  mush.  To  have  them  thin  the  egg 
was  omitted  until  after  boiling,  when  it  was  added  to  the 
cooled  mass.  The  amounts  injected  varied  from  25  c.c. 
to  90  c.c,  which  was  about  sufficient  to  fill  the  large  bowel 
of  the  animals  experimented  upon. 

Besides  depending  upon  mere  observation,  radiographs 
were  taken  at  various  intervals,  in  order  to  show  the  dis- 
tribution of  the  injected  enemas.  After  a  control  radio- 
graph had  shown  the  absence  of  any  bismuth-containing 
food  in  the  intestine  of  the  animal  to  be  experimented  upon, 
the  food  was  introduced  into  the  rectum.  It  was  found 
in  these  experiments  that  when  only  small  amounts  are 
injected  they  lie  at  first  in  the  descending  colon.  In  every 
case,  however,  anti-peristaltic  waves  commence  and  the 
food  is  carried  through  the  transverse  and  ascending  colon 
into  the  caecum.  Small  injections  of  nutrient  material 
never  pass  this  point.  The  larger  injections,  however,  do 
not  stop  when  they  reach  the  ileocaecal  valve,  but  pass  through 
it  high  up  into  the  small  intestine.  Strange  as  it  may  seem, 
this  valve,  which  is  competent  to  the  food  passing  through 
it  in  the  normal  progress  of  the  food  from  the  stomach  to 
the  rectum,  allows  the  nutrient  material  from  large  rectal 
enemas  to  pass  through  into  the  small  intestine.  The  anti- 
peristaltic waves  of  the  ascending  colon  seem  to  be  the 
effective    agents   in    forcing   the  enema    backward    through 


54  PHYSIOLOGY  OF  ALIMENTATION. 

the  ileocecal  valve  and  along  the  ileum,  for  when  the  valve 
first  allows  the  food  to  pass  through,  it  pours  into  the 
small  intestine  and  appears  as  a  mass  which  suddenly  fills 
several  loops  of  the  gut.  Anti-peristalsis  does  not  appear 
in  the  small  intestine  though  it  continues  in  the  large.  After 
the  food  has  been  in  the  small  intestine  for  some  time,  the 
typical  segmenting  movements  appear,  which  divide  and 
redivide  the  food  in  the  manner  already  described  above. 

Figs.  15,  16,  and  17  are  radiographs  which  indicate  how 
the  food  is  forced  after  a  large  enema  more  and  more  from 
the  large  intestine  into  the  small.  An  enema  of  90  c.c. 
was  given  at  1.40  p.m.  The  first  radiograph  shows  how 
at  1.50  p.m.  the  food  is  evenly  distributed  through  the  large 
intestine  and  through  several  loops  of  small  intestine.  In 
the  second  and  third  radiographs,  taken  at  2.15  and  3.00  p.m. 
respectively,  the  food  is  seen  to  have  left  the  large  intestine  to 
a  great  extent,  and  to  be  occupying  an  increasingly  greater 
number  of  loops  of  small  intestine.  Observations  made  at 
3.00  p.m.  showed  segmentation  to  be  going  on  in  many 
of  the  loops. 

The  importance  of  the  ascending  and  transverse  portions 
of  the  large  intestine  as  an  absorptive  organ  has  already 
been  pointed  out,  and  it  is  not  surprising,  therefore,  to  find 
evidences  of  this  same  absorption  when  food  is  introduced 
into  the  intestinal  tract  by  way  of  the  rectum.  In  the 
region  of  the  anti-peristaltic  waves  in  the  large  intestine  the 
shadows  become  progressively  lighter,  until  in  the  end  the 
bismuth  seems  to  be  covering  only  the  walls  of  the  gut. 
In  the  descending  colon  the  shadows  retain  their  original 
opacity.  When  the  rectal  injections  are  large,  the  small 
intestine  also  comes  into  play  as  an  absorptive  organ,  and 
this  in  the  same  way  apparently  as  when  the  food  is  intro- 
duced through  the  mouth. 

It  must  be  pointed  out,  finally,  that  if  any  digestive  juices 
are  present  in  the  large  and  small  intestines,  these  are  of 
course  mixed  with  the  nutrient  enemas  and  so  are  given  an 


I'm.  1. 


(From  an  x-ray  photograph  kindly  senl  me  by  Dr.  Cannon. 


.-,:, 


Fig.  Hi.    2.15  p.m. 
(From  an  rc-ray  photograph  kindly  sent  me  by  Dr.  Cannon. 


Fig.  17.    3.00  p.m 
<  From  an  x-ray  photograph  kindly  Bent  me  by  Dr.  t'w 


MECHANICAL  PIIEXOMENA.  61 

opportunity  of  exerting  their  specific  effects.  How  much  of 
such  a  secretion  occurs,  and  its  quality,  can,  however,  only 
be  surmised.  If  no  food  has  been  introduced  through  the 
mouth,  and  no  "psychic"  or  other  secretion  from  the  stomach 
lias  in  consequence  been  called  forth,  little  or  no  pancreatic 
or  intestinal  juice  of  any  kind  may  be  present  in  the  intes- 
tine. This  urges  upon  us  the  necessity  of  introducing  into 
the  rectum  only  those  foods  which  can  be  taken  up  directly  by 
the  lower  portions  of  the  alimentary  tract.  Certain  foods 
are  already  in  this  condition,  while  others  must  first  be 
digested  outside  of  the  body,  or  have  introduced  along  with 
them  those  ferments  which  are  found  in  the  body  and  are 
capable  of  so  acting  upon  the  various  constituents  of  the 
nutrient  enemas  that  they  are  converted  into  readil}7  absorb- 
able substances.  Unless  this  chemical  side  of  rectal  feeding 
is  considered,  we  must  fail  in  the  objects  which  we  wish  to 
attain  by  these  artificial  means. 


CHAPTER  III. 

THE  JUICES  POURED  OUT  UPON  THE  FOOD   AND  THEIR 
CHEMICAL  CONSTITUENTS. 

I.  The  Saliva. — This  is  the  name  applied  to  the  mixed 
secretions  from  the  salivary  glands  and  the  mucous  glands 
of  the  mouth.  The  salivary  glands  are  three  in  number, 
the  parotid,  submaxillary,  and  sublingual,  and  as  their  secre- 
tions differ  somewhat  they  are  best  considered  separately. 

Human  parotid  saliva  can  be  obtained  by  introducing  a 
fine  cannula  into  Stenson's  duct.  In  this  way  a  clear,  watery 
liquid  mixed  with  some  epithelial  cells  and  occasionally  a 
few  leucocytes  is  obtained.  The  reaction  is  usually  given 
as  faintly  alkaline,  but  this  seems  to  be  incorrect.  It  is 
probably  neutral,  perhaps  even  slightly  acid. 

The  amount  secreted  in  twenty-four  hours  varies  within 
wide  limits  physiologically.  Ohl  gives  80  to  100  c.c.  The 
specific  gravity  varies  under  physiological  conditions  and  is 
stated  to  be  between  1.006  and  1.012.  The  parotid  secretion 
contains  mucin  and  only  traces  of  proteins.  It  contains  the 
starch-splitting  ferment  amylase  and  the  maltose-splitting 
ferment  maltase.  It  also  contains  sulphocyanic  acid  in  com- 
bination with  the  metals  found  universally  in  the  tissue 
fluids.  The  exact  amount  of  each  of  these  substances  varies 
under  physiological  conditions,  so  that  it  is  not  surprising 
that  the  figures  given  by  different  investigators  do  not  agree 
very  well.  Mitscherlich  found  14  to  16  parts,  Hoppe- 
Seyler  about  7  parts  of  solids  in  1000  of  parotid  saliva. 
About  half  of  this  amount  is  organic,  the  rest  inorganic. 

62 


Tin:  JUICES  POURED  OUT  UPUS   THE  food.      63 

Potassium  sulphocyanate  is  present  to  (lie  extent  of  about 
3  parts  in  I0.000.1 

Human  submaxillary  saliva  may  bo  obtained  in  :i  way 
similar  to  that  described  above  for  obtaining  parotid  saliva, 
namely,  insertion  of  a  fine  cannula  into  Wharton's  duct. 
When  the  sublingual  gland  does  not  open  into  the  mouth  by 
a  separate  duct,  but  discharges  its  secretion  into  Wharton's 
duct,  the  two  secretions  can  be  separated  by  pushing  the 
cannula  far  enough  along  the  common  duct  to  pass  beyond 
the  opening  from  the  sublingual  gland.2  The  secretion  ob- 
tained in  this  way  is  clear  and  watery  and  of  a  specific 
gravity  somewhat  lower  than  that  of  the  parotid.  It  is 
variously  stated  to  be  from  1.0026  to  1.0250,  and  is  subject  to 
considerable  variation  under  physiological  conditions.  The 
amount  of  solids  contained  in  the  submaxillary  saliva  is 
between  4  and  5  parts  in  1000,  against  6  to  15  parts  found 
in  parotid  saliva.  The  character  of  the  solid  constituents 
is  much  the  same  as  in  the  parotid  saliva,  except  sulpho- 
cya  nate,  the  presence  of  which  is  questioned  by  some  authors. 
Sulphocyanate  is  certainly  present  in  less  amount  in  the 
submaxillary  secretion  than  in  the  parotid.  This  amount  as 
well  as  the  quantity  of  submaxillary  saliva  secreted  in  any 
unit  of  time  varies  greatly  under  physiological  conditions. 
Roughly  speaking,  the  total  amount  secreted  in  twenty- 
four  hours  is  three  times  as  great  as  that  secreted  by 
the  parotid  (Ohl).3  The  reaction  is  generally  stated  to 
be  alkaline,  more  probably,  however,  it  is  neutral.  The 
starch-splitting  activity  of  the  submaxillary  saliva  is  very 
great. 

Ohl  seems  to  be  the  only  investigator  who  ever  obtained 
human  sublingual  saliva  in  sufficient  amount  to  determine 
thai  it  contains  amylase,  sulphocyanate,  and  mucin. 

lVlBRORDT.    lal'illcn,  .leiKi,  1X88,  p.  30. 

2  See  Moore:  Text-book  of  Physiology,  edited  by  Schaefer,  Edin- 
burgh, 1898, 1,  p.  312. 

3  Vierordt:  Tabellen,  Jena,  1888,  p.  130. 


64  PHYSIOLOGY  OF  ALIMENTATION. 

The  mucous  glands  of  the  mouth  secrete  a  small  amount  of 
an  exceedingly  tenacious  material  containing  much  mucin. 
This  secretion  has  never  been  obtained  pure  in  the  human 
being,  but  experimentally  it  has  been  gotten  from  dogs  after 
ligature  of  the  ducts  or  extirpation  of  the  entire  set  of  salivary 
glands.  The  secretion  is  mixed  with  many  epithelial  cells 
from  the  mouth. 

The  mixed  saliva  is  that  usually  employed  for  experimental 
purposes.  The  amount  of  this  secretion  in  twenty-four  hours 
is  stated  by  Bidder  and  Schmidt  1  to  be  300  to  1500  c.c.  The 
quantity  secreted  in  the  unit  of  time  is  largest  during  meals 
and  falls  to  a  minimum  between  meals.  These  variations  will 
be  discussed  in  greater  detail  later.  The  mixed  saliva  froths 
easily  and  is  somewhat  turbid,  from  admixture  with  epithelial 
cells  and  some  leucocytes,  together  with  the  mucin  obtained 
chiefly  from  the  mucous  glands  of  the  mouth.  The  saliva 
contains  vast  numbers  of  bacteria.2  The  average  specific 
gravity  is  1.003  to  1.004.  The  reaction  is  ordinarily  stated 
to  be  alkaline,  but  recent  observations  seem  to  indicate 
that  it  is  neutral,  perhaps  even  acid,  in  reaction.  That  saliva 
is  able  to  neutralize  strong  acids  does  not  indicate  that  this 
secretion  is  alkaline  in  reaction,  but  simply  that  it  contains 
salts  of  strong  bases  combined  with  weak  acids,  such  as  car- 
bonates and  bicarbonates. 

Toward  litmus,  lacmoid,  and  rosolic  acid  saliva  reacts  as 
though  it  were  alkaline.  When  phenolphthalein  is  used,  how- 
ever, the  solution  remains  colorless.  Ten  cubic  centimeters  of 
mixed  saliva  require  0.2  c.c.  of  a  1/10  normal  alkali  solution 
before  the  phenolphthalein  will  just  turn'  pink,  indicating  an 
alkaline  reaction.  Saliva  is  therefore  to  be  considered  as  at 
least  neutral,  if  anything  else,  slightly  acid,  for  phenolphthalein 
is  in  this  case  to  be  looked  upon  as  a  more  reliable  indicator 
than  any  of  the  others  mentioned  above.     What  holds  for  the 

1  Vierordt*.  Tabellen,  Jena,  1888,  p.  128. 

2  See  p.  160. 


THE  JUICES  POURED  OUT   UPON   THE  FOOD.        65 

ordinary  mixed  human  saliva  is  true  also  of  the  saliva  ob- 
tained from  the  dog  after  stimulation  of  the  chorda  tympani 
nerve  or  after  poisoning  with  curare.1 

Among  the  inorganic  constituents  of  the  saliva  are  the 
chlorides,  carbonates,  bicarbonates,  phosphates,  and  sul- 
phates of  sodium,  potassium,  magnesium,  and  calcium.  The 
escape  of  carbon  dioxide  from  the  saliva  on  standing  allows 
the  precipitation  of  the  bicarbonate  of  calcium  as  the  car- 
bonate. This  substance  is  the  chief  constituent  of  salivary 
calculi  and  "tartar." 

Much  importance  was  at  one  time  attached  to  the  quanti- 
tative determination  of  the  sulphocyanate  in  the  saliva  as 
an  indicator  of  the  rate  of  protein  metabolism,  for  it  is  gener- 
ally believed  that  this  substance  is  a  product  of  protein  me- 
tabolism. Moore,  however,  believes  that  its  estimation  is  of 
little  value. 

The  gases  of  the  saliva  are  oxygen,  nitrogen,  and  carbon 
dioxide.  The  latter  predominates,  and  is  found  chiefly  in 
chemical  combination. 

Among  the  organic  constituents  of  the  saliva  the  ferments 
amylase  and  maltase  are  of  the  greatest  importance.  The 
former  of  these  two  is  characterized  by  its  action  upon  starches 
which  are  under  its  influence  converted  into  maltose.  Mal- 
tase is  especially  effective  in  causing  a  still  further  cleavage 
of  this  sugar  into  dextrose.  While  food  is  being  chewed, 
therefore,  and  for  some  time  after  it  reaches  the  stomach,  the 
starches  contained  in  it  are  undergoing  a  change  which  con- 
verts them  into  substances  readily  absorbed  by  the  alimentary 
tract.  The  mucin  contained  in  the  saliva  is  probably  of 
little  more  than  mechanical  use  in  supplying  food  with  a 
coating  which  allows  the  more  ready  passage  into  and 
through  the  oesophagus. 

The  oesophagus  itself  is  studded  with  small  mucous  glands 
which  secrete  a  small  amount  of  a  ropy  fluid  rich  in  mucin. 

1  See  Munk:  Centralblatt,  fur  Physiologie,  1902,  XVI,  p.  33. 


66  PHYSIOLOGY  OF  ALIMENTATION. 

The  function  of  this  secretion  is,  so  far  as  known,  purely 
mechanical,  in  that  it  serves  to  lubricate  the  bolus  of  food  as 
it  passes  through  this  tube. 

2.  The  Gastric  Juice  is  the  term  applied  to  the  secretion 
of  the  mucosa  of  the  stomach.  Absolutely  pure  gastric  juice 
can  be  obtained  from  human  beings  only  in  small  quan- 
tities, impure  juice  in  somewhat  larger  quantities.  Pure 
juice  has  been  obtained  in  cases  of  gastric  fistula.  Most  ob- 
servations are  based  upon  a  study  of  the  impure  juice  ob- 
tained by  feeding  meals  of  known  composition  and  then 
evacuating  the  contents  through  a  stomach-tube  or  a  fistula 
if  such  exists. 

Pure  gastric  juice  is  best  obtained  from  the  dog  by  the 
method  of  "sham  feeding  "  of  Pawlow  and  Schumow-Siman- 
owsky.1  This  consists  in  feeding  a  dog  in  which  the  oesoph- 
agus has  been  separated  in  such  a  way  from  the  stomach 
that  the  food  never  really  enters  the  stomach.  When  such 
sham  feeding  is  carried  out,  a  reflex  secretion  of  pure  gastric 
juice  occurs.  Such  a  sham  feeding  may  be  kept  up  without 
injury  to  the  dog  for  an  hour  daily,  in  the  course  of  which 
time  200  to  300  c.c.  of  juice  may  be  collected.  The  quantity 
secreted  in  twenty-four  hours  is  subject  to  great  variations, 
but  amounts  to  about  1/15  to  1/10  the  body  weight  in  dogs. 
If  we  assume  that  the  same  proportion  exists  between  the 
amount  of  the  gastric  juice  and  the  body  weight  in  the  case 
of  the  human  being,  a  man  weighing  70  kilos  would  secrete 
4  to  7  liters  daily. 

Konowaloff  2  describes  the  gastric  juice  obtained  from  the 
dog  by  sham  feeding  as  a  clear,  colorless,  odorless  liquid  of  a 
specific  gravity  averaging  1.00478.  The  acidity  given  by 
Konowaloff  is  higher  than  that  of  any  other  author,  0.544 
percent  of  hydrochloric  acid.     A  figure  approximating   this 

1  See  Chapter  XI,  Part  1.  Pawlow  and  Schumow-Simanowsky: 
Centralbl.  f.  Physiol.,  1889,  III,  p.  113.  Pawlow:  Work  of  the 
Digestive  Glands.     Trans,  by  Thompson,  London,  1903,  p.  12, 

2  Pawlow:  1.  c. 


THE  JUICES  POURED  OUT  UPON   THE  FOOD.       07 

value  was  obtained  long  ago  by  Hkideniiain.  In  spite  of  the 
majority  of  observations  to  the  contrary,  this  high  acidity 
probably  represents  the  true  value  under  physiological  con- 
ditions. Because  of  this  acidity,  bacteria  do  not  develop 
well  in  gastric  juice,  and  it  may  in  consequence  be  kept  for 
a  long  time  without  undergoing  decomposition.  The  acidity 
of  the  normal  gastric  juice  is  due  to  hydrochloric  acid.  This 
was  first  proved  by  Prout  and  independently  of  him,  but 
later,  by  Tikdemann  and  Gmelin.  The  objections  which 
were  raised  against  this  idea  by  Claude  Bernard  and  Ber- 
reswil  have  been  set  aside  by  the  researches  of  Schmidt.1 
Traces  of  organic  acids  are  at  times  found  in  the  normal 
gastric  secretion. 

Human  gastric  juice  does  not  differ  in  its  physical  or 
chemical  properties  from  canine  juice.  The  concentration 
of  the  acid  and  the  pepsin  is  perhaps  somewhat  lower  in 
man. 

No  complete  analysis  of  gastric  juice  seems  to  be  at  hand. 
Besides  hydrochloric  acid,  gastric  juice  contains  the  fer- 
ment acid- proteinase  (pepsin),  which  has  the  power  of  acting 
on  proteins  and  splitting  them  into  a  number  of  simpler 
bodies.  Caseinase  (rennin)  is  also  found  in  the  gastric 
juice  of  the  human  being  as  well  as  that  of  other  animals. 
This  ferment  has  the  power  of  curdling  milk.  The  hydro- 
chloric acid  present  in  the  stomach  is  of  itself  able  to 
bring  about  this  change,  but  the  presence  of  the  ferment 
can  be  demonstrated  by  neutralizing  the  gastric  juice 
with  an  alkali,  when  it  is  found  that  the  milk-curdling 
power  still  persists.  It  is  lost,  however,  when  the  neutral 
gastric  juice  is  heated  to  70°  C.  for  a  short  time.  The 
secretion  of  the  stomach  also  contains  a  fat-splitting  fer- 
ment, lipase  (steapsin),  but  its  physiological  importance 
is  probably  small,  as  the  ferment  acts  little  or  not  at  all 


1  For  an  interesting  account  of  the  subject,  see  Mooke:  Text-book  of 
Physiology,  edited  by  Sciiai  :i  i.i;    Kdinburgh,  1S(JS,  1,  p.  351. 


68  PHYSIOLOGY  OF  ALIMENTATION. 

in  an  acid  medium  of  the  concentration  found  in  the  stomach. 
A  substance  which  is  obtained  as  a  coagulum  from  gastric 
juice  on  boiling  probably  represents  the  combined  ferments, 
together  with  mucin  and  traces  of  organic  material  derived 
from  particles  of  digested  food  or  the  dead  cells  of  the 
stomach-wall  itself. 

The  wall  of  the  stomach  contains  the  antiproteinase  (anti- 
pepsin)  discovered  by  Weinland.  As  its  name  indicates, 
this  substance,  when  present,  prevents  the  proteolytic  fer- 
ments from  acting.  As  it  is  probably  due  to  the  presence 
of  this  substance  in  the  wall  of  the  stomach,  and  in  the  in- 
testines, that  the  alimentary  tract  does  not  digest  itself,  it 
will  be  discussed  in  some  detail  later.1 

The  inorganic  constituents  of  the  gastric  juice  exclusive  of 
the  hydrochloric  acid  consist  of  the  chlorides  and  traces 
of  the  phosphates  of  sodium,  potassium,  magnesium,  cal- 
cium, -iron,  and  ammonium.  The  only  figures  indicative 
of  the  quantities  in  which  these  exist  in  the  gastric  juice 
are  based  upon  analyses  of  the  impure  secretion  or  such 
as  was  obtained  under  other  than  physiological  conditions. 
As  these  are  practically  valueless,  they  will  not  be  given 
here. 

The  action  of  the  ferments  of  the  gastric  juice,  and  the 
variations  in  its  composition  and  quantity,  will  be  discussed 
further  on. 

3.  The  Pancreatic  Juice. — The  quantity  of  juice  which 
flows  from  the  pancreas  varies  greatly  in  different  animals 
and  in  the  same  animal  under  different  physiological  con- 
ditions. The  observations  of  the  older  investigators  are 
probably  very  incorrect.  Pawlow  and  his  coworkers  state 
that  the  amount  of  normal  juice  which  can  be  obtained 
from  a  dog  possessing  a  permanent  fistula2  is  21.8  c.c.  per 
kilo  in  twenty-four  hours.  The  pancreatic  juice  from  a 
dog  is  a  clear,  colorless,  odorless  liquid,  somewhat  variable 

1  See  p.  133.  2  See  Chapter  XII,  Part  1. 


THE  JUICES  POURED   OUT   UPON    THE  FOOD.        60 

in  composition  and  often  containing  enough  protein  to 
coagulate  into  a  solid  when  heated. 

The  purest  and  apparently  normal  human  pancreatic  juice 
has  been  obtained  by  Glaessner  *  from  a  forty-six  year  old 
woman  possessing  a  fistula  of  the  pancreatic  duct.  Glaessner 
describes  it  as  a  water-like  liquid  which  froths  easily  and 
on  standing  shows  a  very  slight  sediment.  The  juice  has  a 
decided  alkaline  reaction  even  toward  phenolphthalein,  so 
that  it  may  really  be  regarded  as  alkaline  in  reaction. 
Analysis  of  two  specimens  showed  respectively  1.2708  and 
1.2404  parts  of  dry  substance  in  100  of  the  juice.  Analysis 
of  the  dry  substance  showed,  besides  the  ordinary  inorganic 
salts,  albumin,  albumose,  and  peptone.  Glaessner  gives  as 
the  specific  gravity  of  the  juice  1.00748. 

The  quantity  of  juice  secreted  by  Glaessner 's  patient  in 
twenty-four  hours  varied  from  day  to  day,  the  extremes 
being  420  and  848  c.c.  The  quantity  as  well  as  the  quality 
varied  with  the  character  of  the  food  ingested.  During 
starvation  the  quantity  was  very  low,  as  was  also  the 
digestive  power  for  proteins,  fats,  and  starch.  Under 
these  conditions  the  alkalinity  was  also  lower  than  after 
feeding.2 

The  pancreatic  juice  contains  several  ferments — alkali- 
proteinase  (trypsin),  lipase  (steapsin),  amylase  (amylopsin), 
caseinase  (rennin),  and  at  certain  times  lactase.  The  alkali- 
proteinase  is  able  to  act  upon  proteins  and  to  split  them 
into  a  series  of  simpler  substances  in  a  manner  similar  to 
but  more  powerful  than  acid-proteinase.  Lipase  acts  upon 
fats,  breaking  these  up  into  fatty  acid  and  alcohol.  The 
amylase  of  the  pancreas  is  similar  to  that  of  the  saliva,  and 
through   its    action  on   starch   brings    about   the   formation 


1  Glaessnek.  Zeitschrift  fur  physiologische  Chemie,  1904,  XL,  p.  465. 
For  a  review  of  the  older  literature  on  human  pancreatic  juice,  see 
Schumm:    Zeitschrift  fur  physiologische  Chemie,  1901.',  XXXYl ,  p,  292, 


70  PHYSIOLOGY  OF  ALIMENTATION. 

of  maltose  and  dextrin.  Caseinase  is  the  name  given  to 
the  milk-curdling  ferment  of  the  pancreas.  It  is  similar 
to  the  milk-curdling  ferment  of  the  stomach.  Lactase  is 
present  in  the  pancreas  only  at  certain  periods  in  the  life 
of  an  animal  and  under  certain  conditions.  It  is  found 
normally  in  the  pancreatic  secretions  of  the  puppy  during 
the  period  of  lactation.  In  adult  dogs  it  is  absent,  but  it 
can  be  made  to  appear  again  if  the  dog  is  kept  for  some 
time  on  a  milk  diet  or  any  diet  containing  milk-sugar.  This 
ferment  has  the  power  of  acting  upon  milk-sugar  (lactose) 
and  converting  it  into  dextrose  and  galactose.  A  detailed 
discussion  of  these  ferments  is  given  further  on.1 

It  is  as  yet  not  entirely  settled  whether  the  ferments  are 
secreted  as  such  from  the  pancreas  or  as  proferments.  Ac- 
cording to  Delezenne,  Frouin,  and  Popielski,2  the  juice  as 
collected  directly  from  the  pancreatic  duct  never  contains 
alkali-pro teinase  (trypsin),  but  only  its  proferment  (tryp- 
sinogen).  This  yields  alkali-pro  teinase,  however,  as  soon  as 
it  flows  over  the  mucous  membrane  of  the  duodenum,  where 
it  encounters  enterokinase.3  Whether  similar  conditions  hold 
for  the  other  ferments  is  a  matter  of  dispute. 

In  human  pancreatic  juice  Glaessner  could  find  no  alkali- 
proteinase  (trypsin),  but  only  the  proferment,  which  could, 
however,  be  converted  into  alkali-proteinase  by  adding  to 
it  an  extract  (enterokinase)  of  the  mucous  membrane  of  the 
small  intestine  obtained  from  human  corpses.  Both  lipase 
and  amylase  were  also  found,  but  no  maltase,  sucrase,  or 
lactase,  a  fact  which  agrees  well  with  experimental  findings 
in  animals. 

4.  The  Bile  is  the  name  given  to  the  secretion  from  the 
liver  which  is  poured  into  the  duodenum  through  the  com- 


1  See  Chapters  IV,  V,  VI,  VII,  and  VIII. 

2  Delezenne  and  Frouin.  Comptes  rendus  de  l'acad.,  CXXXIV,  p. 
1526;  Comptes  rendus  de  Soc.  biol.,  LlV,  p.  691;  Popielski.  Central- 
blatt  fur  Physiologie,  XVII,  p.  65. 

3  See  Chapter  XIII,  Part  4. 


THE  JUICER  POURED  OUT   UPON    THE   FOOD         71 

mon  duct.  The  quantity  of  bile  secreted  in  twenty-four 
hours  varies  not  only  in  different  animals  but  in  the  same 
animal  under  different  circumstances.  Contrary  to  the 
generally  accepted  view,  the  secretion  of  bile  is  nol  con- 
tinuous and  of  varying  intensity,  that  is  to  say,  remittent, 
but  intermittent.  During  certain  periods  no  bile  whatsoever 
escapes  into  the  intestine.  According  to  von  Wittich  and 
Westphalen,  the  total  amount  of  bile  secreted  by  a  human 
being  in  twenty-four  hours  is  about  500  c.c.1  These  obser- 
vations were  made  on  two  men  having  biliary  fistula).  The 
specific  gravity  of  the  bile  is,  according  to  Westphalen, 
1.0104.  In  100  parts  of  liquid  bile  are  contained  2.253 
parts  of  solids. 

All  these  figures  must  be  looked  upon  as  only  approxi- 
mately correct.  Later,2  when  the  quantitative  and  quali- 
tative variations  in  the  secretion  of  the  bile  are  discussed, 
the  reason  for  this  will  be  more  apparent.  This  explains 
also  why  the  figures  of  scarcely  any  two  of  the  score  of 
observers  who  have  worked  on  the  biliary  secretion 
agree. 

The  bile  consists  of  the  secretions  of  the  liver-cells  them- 
selves, mixed  with  the  mucus  which  is  secreted  by  the  bile- 
channels  and  the  gall-bladder.  As  the  bile  passes  from  the 
liver-cells  toward  the  intestine  it  undergoes  a  change,  the 
bile  from  the  gall-bladder  and  lower  bile-passages  being 
somewhat  more  viscid,  because  of  loss  of  water  and  ad- 
mixture with  mucus,  and  cloudier,  because  of  the  presence 
of  cells  and  cellular  debris,  than  that  collected  from  the  bile- 
passages  higher  up.  The  color  of  the  bile  is  different  in 
different  animals,  and  in  the  same  animal,  depending  upon 
the  conditions  under  which  it  has  been  obtained.  Human 
bile  obtained  immediately  alter  death  has  a  golden-yellow, 
brownish-yellow,  or  at  times  slightly  greenish  color.     That 

*  Viekoudt:  Tabellcn,  Jena,  188S,  p.  135. 
*See  Chapter  XIII,  I 'art  1. 


72  PHYSIOLOGY  OF  ALIMENTATION. 

obtained  at  an  ordinary  post-mortem  is  yellowish  brown, 
brown,  or  green.  The  reaction  of  the  bile  is  ordinarily 
stated  to  be  alkaline.  It  is  probable,  however,  that  it  is 
neutral. 

The  most  important  constituents  of  the  bile  besides  water 
are  the  bile  acids  in  combination  with  the  alkali  metals,  and 
the  bile  pigments.  Among  the  other  important  constituents 
are  the  inorganic  salts  which  are  universally  present  in  the 
body  and  fats,  lecithin,  cholesterin,  urea,  and  soaps. 

The  bile  acids  are  several  in  number  and  are  usually  divided 
into  the  glycocholic  and  taurocholic  groups,  each  of  which  has 
several  members.  The  bile  pigments  are  also  several  in  num- 
ber. The  reddish-yellow  bilirubin  and  the  green  biliverdm 
are  always  present  in  bile  under  physiological  conditions. 
Hydrobilirubin  perhaps  also  belongs  to  this  group.  Under 
pathological  conditions,  as  in  gall-stones,  a  number  of  other 
pigments  besides  those  already  mentioned  may  be  found, 
of  which  choletelin,  bilifuscin,  biliprosin,  bilihumin,  and 
bilicyanin  are  the  most  important.  Bilirubin  and  hydro- 
bilirubin are  of  great  physiological  interest  because  of  the 
identity  or  at  least  close  chemical  relation  of  the  former  to 
a  derivative  of  haemoglobin,  hsematoidin,  and  of  the  latter  to 
urobilin,  one  of  the  urinary  pigments. 

The  inorganic  constituents  of  the  bile  comprise  the  chlo- 
rides, phosphates,  and  sulphates  of  sodium,  potassium,  cal- 
cium, magnesium,  iron,  and  copper.  Urea  is  found  only  in 
traces.  The  following  three  analyses  of  human  bile  by 
Hammarsten,1  which  probably  are  as  trustworthy  as  any  at 
our  disposal,  will  give  an  idea  of  the  relative  proportions  in 
which  the  various  constituents  exist  in  this  secretion.  The 
figures  indicate  parts  per  1000. 

Water 974.800         964.740         974.600 

Solids 25.200  35.260  25.400 

i  Hammarsten:  Text-book  of  Physiological  Chemistry.  Translated 
by  Mandel,  New  York,  1904,  p.  276. 


THE  JUICES  POURED  OUT    UPON   THE  FOOD        73 

The  latter  consist  of: 

Mucin  and  pigments 5.290  4.290  5.150 

Taurodiolate  salts 3.034  2.079  2.180 

Glycocholatc  salts 6.276  10.161  6.S60 

Fatty  acids  from  soaps.  ...  1 .  230  1 .  300  1.010 

Cholestcrin 0.630  1.600  1.500 

Lecit  hin  \  /  0    17".  0 .  650 

Fat          J   10.956  0  610 

Soluble  mineral  salts 8.070  6.760  7.250 

Insoluble  mineral  salts 0 .  250  0 .  490  0  210 

The  functions  of  the  bile  and  the  regulation  of  the  biliary 
flow  can  be  better  discussed  elsewhere.1 

5.  The  Intestinal  Juice. — Under  this  heading  are  grouped 
all  the  secretions  of  the  intestine  proper  from  the  pylorus 
of  the  stomach  to  the  anus.  The  intestinal  juice  has  been 
obtained  in  man  from  cases  of  intestinal  fistula;  from  animals 
it  is  obtained  experimentally  and  unmixed  with  other  diges- 
tive secretions  or  food  by  the  production  of  either  a  Thiry 
or  a  Vella  fistula  in  any  desired  portion  of  the  small  or  large 
intestine.2 

The  pure  juice  obtained  from  different  portions  of  the 
intestinal  canal  below  the  stomach  varies  not  only  in  amount 
but  also  in  composition.  We  shall  first  consider  the  secre- 
tion of  the  small  intestine  (succus  entericus).  Rohmann3 
describes  the  juice  0}  the  small  intestine  of  the  dog  as  scant}' 
in  amount,  viscid,  and  somewhat  gelatinous  in  the  upper 
portions,  and  as  larger  in  amount  and  more  fluid  in  the  lower 
portions.  Thiry  4  obtained  a  maximum  secretion  of  4  c.c- 
per  hour  from  a  loop  of  small  intestine  having  a  total  sur- 
face of  30  sq.  cm.  The  specific  gravity  is  given  by  the 
same  author  as  1.0115,  and  the  juice  is  described  as  clear, 
light  yellow,  somewhat  opalescent,  and  of  a  decided  alka- 
line reaction.     The  juice  from   the  small  intestine  contains 

1  See  Chapter  XIII,  Parts  I  and  2. 

1  See  Chapter  XIII,  Pari  3. 

8  Rohmann.  Pfluger's  Archiv,  1887,  XL1,  p.  424. 

4  Thiry.   Vieroult's  TaKcllen,  Jena,  1S88,  p.  140. 


74  PHYSIOLOGY  OF  ALIMENTATION. 

protein,  mucin,  urea,  and  the  ordinary  salts  found  every- 
where in  the  secretions  and  tissues  of  the  body.  The  amount 
of  carbonate  is  particularly  high,  to  which  fact  the  alkaline 
reaction  of  the  juice  is  attributed. 

The  descriptions  given  of  the  secretion  of  the  small  in- 
testine in  the  human  being  are  practically  the  same  as  those 
given  above  for  the  juice  obtained  from  dogs.  The  best 
observations  on  human  intestinal  juice  are  those  of  Tubby 
and  Manning,1  Hamburger  and  Hekma,2  and  Nagano.3  In 
Tubby  and  Manning's  case  pure  intestinal  juice  was  obtained 
from  a  piece  of  intestine  3 J  inches  long  situated  some  8  inches 
above  the  ileocsecal  valve.  Their  description  of  the  juice 
is  similar  to  that  of  other  observers  and  may  be  taken  as  a 
type.  The  daily  yield  of  juice  from  this  piece  of  intestine 
varied  from  19  to  35  c.c;  the  specific  gravity  from  1.0016 
to  1.0162,  on  the  average  1.0069.  The  fluid  was  opalescent, 
and  on  standing  a  sediment  consisting  of  leucocytes  and 
desquamated  intestinal  epithelium  formed.  The  juice  gave 
a  strong  alkaline  reaction,  and  contained  protein,  mucin, 
and  the  ordinary  salts,  of  which  the  carbonates  and  chlo- 
rides of  sodium  and  potassium  were  the  more  conspicuous. 

Within  the  last  few  years  our  conceptions  of  the  nature 
of  the  chemical  substances  contained  in  the  secretions  of 
the  intestine  and  in  the  walls  of  this  portion  of  the  alimentary 
tract  have  undergone  great  revision,  and  from  having  looked 
upon  this  chapter  of  alimentation  as  comparatively  unim- 
portant we  now  rank  it  with  chapters  on  the  pancreas  and 
stomach.  This  is  due  to  the  discovery  in  the  intestinal 
juice  and  in  the  walls  of  the  intestine  of  a  number  of  new 
chemical  substances,  an  understanding  of  the  functions  of 
which,  together  with  a  proper  appreciation  of  the  physio- 

'  Tubby  and  Manning:  Guy's  Hospital  Reports,  London,  1891, 
XLVIII    P-  277. 

-  Hamburger  and  Hekma-  Journal  de  Physiol.,  IV.  p  805. 

'Nagano:  Mittheilungen  aus  den  Grenzgebieten  der  Medicin  und 
Chirurgie.  IX,  p.  393. 


THE  JUICES  POURED  01  T  UPON    THE    FOOD        75 

logical  importance  of  (hose  already  well  known,  has  given  us 
a  new  insight  into  the  importance  of  the  small  intestine  in 
the  great  problem  of  alimentation.  The  following  is  a  list 
of  these  chemical  substances,  together  with  a  brief  indication 
of  their  physiological  functions,  which  are  discussed  in  grea  ter 
detail  later. 

Proteinase.  This  ferment  is  found  in  the  secretion  and 
mucous  membrane  of  the  duodenum  and  originates  from 
the  glands  of  Brunner,  found  in  this  section  of  the  intestine. 
It  seems  to  be  identical  with  the  acid-proteinase  of  the 
stomach,  as  it  acts  best  in  an  acid  medium.  It  is  evident 
that  some  opportunity  is  given  this  ferment  to  aid  in  the 
digestion  of  proteins.  But  as  compared  with  the  activity  of 
the  stomach,  or  pancreas,  that  of  the  duodenum  is  probably 
only  small. 

Protease  (erepsin)  is  one  of  the  most  important  ferments 
found  in  the  intestinal  juice.  This  ferment,  discovered  by 
Cohxiieim,  has  no  action  upon  "native"  proteins  except 
casein,  but  has  the  power  of  splitting  proteoses  and  pep- 
tones into  a  number  of  simpler  substances  (mono-  and 
diamino  acids,  ammonia,  etc.)  which  are  similar  to  those 
formed  through  the  action  of  either  acid-  or  alkali-pro- 
teinase  on  proteins.  Protease  must  therefore  not  be  con- 
founded with  the  proteolytic  ferments  of  either  the  stomach 
or  pancreas.  The  presence  of  this  ferment,  in  human  in- 
testinal juice  has  been  proved  by  Hamburger  and  Hekma. 

Lipase  (steapsin).  It  is  ordinarily  stated  that  lipase  does 
not  occur  in  the  intestinal  juice  or  in  the  mucosa.  The 
experiments  of  Kastle  and  Loevenhart  indicate,  however, 
that  it  is  found  in  all  portions  of  the  mucosa  of  the  small 
intestine  in  sufficient  amounts  to  be  of  the  greatest  impor- 
tance in  the  absorption  of  fats.  The  lipase  of  the  intestine 
is  identical  with  that  of  the  pancreas  and  pancreatic  juice, 
and,  like  the  latter,  splits  fats  into  fatty  acid  and  alcohol. 

Ami/last  is  t'.umd  in  the  small  intestine  and  is  secreted 
in  sufficient  amounts  to  play  an  important  role  in  the  absorp- 


76  PHYSIOLOGY  OF  ALIMENTATION. 

tion  of  starches.  The  ferment  splits  starches  into  malt- 
ose and  dextrin.  Its  presence  in  human  intestinal  juice 
has  been  proved  by  Nagano,  Hamburger  and  Hekma. 

Maltase.  The  occurrence  of  this  enzyme  in  the  small 
intestine  is  still  questioned.  Evidence  is  slowly  accumu- 
lating, however,  to  show  that  it  is  to  the  presence  of  this 
enzyme  in  the  intestinal  juice  and  the  intestinal  mucosa 
that  we  owe  the  splitting  of  the  maltose  formed  from  starch 
into  the  dextrose  found  in  the  intestine  after  the  ingestion 
of  starch  or  malt-sugar.  The  presence  of  a  maltose-splitting 
ferment  in  human  intestinal  juice  is  indicated  by  the  re- 
searches of  Nagano,  Hamburger  and  Hekma. 

Sucrase  (invertase,  invertin)  is  one  of  the  most  important 
enzymes  found  in  the  secretion  of  the  small  intestine.  Cane- 
sugar,  which  serves  as  such  a  common  article  of  diet,  would 
without  the  presence  of  this  enzyme  be  scarcely  absorbed  by 
the  intestine.  The  sucrase  splits  the  cane-sugar  into  the 
readily  absorbable  dextrose  and  lssvulose. 

Lactase  is  found  in  the  intestinal  tract  of  infants  and  those 
adults  who  consume  milk-sugar  either  as  a  separate  article 
of  diet  or  as  one  of  the  constituents  of  milk.  Lactase  acts 
upon  milk-sugar  (lactose)  and  splits  this  into  dextrose  and 
galactose. 

Arginase  is  a  ferment  which  has  recently  been  discovered 
by  Kossel  and  Dakin.  It  has  the  interesting  property  of 
splitting  arginin  into  the  two  chemically  much  simpler  sub- 
stances ornithin  and  urea.  It  is  a  ferment  which  occurs  not 
only  in  the  mucous  membrane  of  the  intestine,  but  also  in  a 
number  of  the  parenchymatous  organs. 

Antiproteinase  (antipepsin  and  antitrypsin).  This  sub- 
stance is  found  in  the  mucosa  of  the  intestine,  but  not  in  the 
secretions  of  the  intestine.  Like  the  antiproteinase  of  the 
stomach,  it  has  the  power  of  preventing  the  proteinases  from 
acting  upon  proteins  and  splitting  them  into  their  well-known 
decomposition-products. 

Enterokinase.      The  ferment  character  of  this  substance 


THE  JUICES  POURED  OUT  UPON   THE  FOOD.        77 

has  not  as  yet  been  entirely  established.  It  is  the  name 
given  by  Pawlow  to  a  substance,  discovered  by  Chepo- 
WALNIKOW  in  the  mucous  membrane  and  secretions  of  the 
small  intestine,  which  has  the  power  of  converting  the 
inactive  proferment  of  the  pancreas  into  the  active  alkali- 
proteinase  (trypsin).  Hamburger  and  Hekma  have  found 
this  substance  in  human  intestinal  juice. 

Pancreatic  Secretin  is  in  no  sense  a  ferment.  It  is  a  term 
applied  by  Bayliss  and  Starling  to  a  substance  formed  in  the 
upper  portion  of  the  intestine  during  digestion,  which  is 
absorbed  into  the  blood  and,  reaching  the  pancreas,  increases 
the  secretion  from  this  gland.1 

The  secretion  of  the  large  intestine  has  been  studied  in  the 
human  being  in  cases  of  fistula  opening  into  the  ascending, 
transverse,  or  descending  portions  of  this  part  of  the  intestinal 
tract,  and  in  animals  in  which  artificial  fistulae  have  been 
created.  The  observations  of  all  who  have  worked  on  the 
secretion  of  the  large  intestine  agree  in  stating  that  it  is  small 
in  amount  and  mainly  composed  of  mucus.  The  juice  is 
alkaline  in  reaction  and  seems  to  contain  no  enzymes  of 
digestive  importance.  It  is  probable,  however,  that  the  food 
which  escapes  through  the  ileocecal  valve,  mixed  with  the 
enzymes  poured  out  upon  it  higher  up  in  the  alimentary  canal, 
continues  to  undergo  digestive  change  in  the  large  bowel.  Of 
greatest  importance  is  the  absorption  which  occurs  in  the 
various  portions  of  the  colon.  While  the  food  is  soft  in  con- 
sistency in  the  ascending  portion  of  the  large  intestine,  it 
becomes  less  liquid  and  finally  firm  as  the  transverse  and 
descending  portions  are  reached,  until  in  the  rectum  the  solid 
faces  are  formed. 

While  no  enzymes  derived  from  the  large  intestine  itself  act 
upon  the  food  in  the  colon,  enzymes  derived  from  the  bacteria 
present  here  bring  about  most  profound  changes  in  the  food. 

1  The  ferments  are  considered  in  greater  detail  in  the  succeeding 
chapters.  Enterokinase  is  discussed  in  Chapter  XHI,  Pari  1.  pan- 
creatic secretin  in  Chapter  XII,  I'art  ■'<. 


78  PHYSIOLOGY  OP  ALIMENTATION. 

These  are  chiefly  of  a  putrefactive  character,  and  affect  in  the 
main  the  protein  constituents  of  the  food.  Certain  of  the 
bacterial  enzymes  belong  to  the  proteinase  group,  and  these 
split  the  undigested  protein  remnants  into  leucin,  tyrosin,  and 
the  other  products  of  proteinase  digestion.  Indol,  skatol, 
and  various  phenols  are  produced  also,  as  well  as  fatty  acids 
(lactic,  butyric,  caproic,  etc.)  and  gases  (hydrogen,  hydrogen 
sulphide,  and  methane). 


CHAPTER  IV. 
FERMENTS  AND  FERMENTATION. 

I.  Organic  Ferments. — Since  ferments,  the  activities  of 
which  we  recognize  in  so  many  physiological  processes,  play  a 
great  role  in  that  special  chapter  of  physiology  with  which 
these  pages  deal,  namely,  alimentation,  it  may  not  be  amiss 
to  discuss  here  their  general  properties. 

Ferments  represent  only  a  special  class  of  the  so-called 
catalytic  agents,  and  are  in  consequence  distinguished  by  the 
same  characteristics  as  catalyzers  in  general.  A  catalyzer  is 
any  substance  which,  without  appearing  in  the  end-products  of  a 
chemical  reaction,  alters  by  its  mere  presence  the  rate  of  this 
chemical  reaction.  The  catalytic  agent  is  therefore  not  to  be 
looked  upon  as  the  cause  of  the  chemical  reaction,  for  this 
occurs  even  in  the  absence  of  the  catalyzer,  only  then  at  a  dif- 
ferent rate.1  When  a  catalytic  agent  increases  the  velocity  of 
a  chemical  reaction  it  is  said  to  be  a  positive  catalyzer;  on  the 
other  hand,  when  it  decreases  the  rate  of  a  chemical  reaction 
it  is  known  as  a  negative  catalyzer.  Examples  of  positive  cata- 
lyzers will  occur  to  everyone.  Common  ones  from  inorganic 
chemistry  are  manganese  dioxide,  which  hastens  the  de- 
composition of  potassium  chlorate  into  potassium  chloride 
and  oxygen  when  heated;  and  nitrogen  tetroxide,  which 
accelerates  the  oxidation  of  sulphurous  acid  into  sulphuric  in 
the  manufacture  of  the  latter  substance.     In  both  instances 

'Ostwald:  liber  Kataly.se,  Leipzig,  1902,  p.  12.  Cohen:  Physical 
Chemistry  for  Physicians.  Translated  by  Martin  H.  Fischer,  New 
York,  1903,  p.  35. 

79 


80  PHYSIOLOGY  OF  ALIMENTATION. 

the  catalyzers  do  not  appear  in  the  end-products,  and  may, 
when  the  reaction  has  been  brought  to  a  standstill,  be  recov- 
ered in  an  unaltered  state.  As  is  well  known,  the  decompo- 
sition of  potassium  chlorate  and  the  oxidation  of  sulphurous 
acid  occur  even  when  the  catalytic  agents  are  not  present, 
but  much  more  slowly. 

Any  of  the  ferments  may  be  cited  as  examples  of  organic 
catalyzers.  We  may  mention  here  lipase,  which  hastens  the 
chemical  decomposition  of  fat  into  fatty  acid  and  alcohol, 
and  proteinase,  which  accelerates  the  rate  of  decomposition 
of  proteins  into  simpler  substances.  Here  also  we  deal  with 
chemical  reactions  which  take  place  even  when  no  ferments 
are  present.  Under  such  circumstances  the  decompositions 
occur  very  slowly,  however,  requiring  weeks,  months,  or 
years  to  attain  the  degree  of  decomposition  which  in  the 
presence  of  the  respective  ferments  may  be  reached  in  a 
few  hours.  As  was  found  to  be  the  case  with  inorganic 
catalyzers,  so  here  also  we  find  that  the  ferments  do  not 
appear  in  the  end-products  of  the  reactions  which  they 
catalyze. 

Examples  of  negative  catalyzers  are  much  more  difficult 
to  discover.  Only  isolated  ones  have  been  described,  and 
since  nearly  all  of  them  seem  now  to  be  regarded  as  inhibitors 
of  positive  catalyzers,  they  will  not  be  discussed  here.  Nega- 
tive organic  catalyzers  are  entirely  unknown,  unless  we  look 
upon  the  antiferments  as  belonging  to  this  group.  Whether 
they  do  or  not  must  be  left  undecided  until  the  mode  of  action 
of  the  antiferments  has  been  discovered.  These  substances 
decrease  markedly  the  velocity  of  certain  chemical  reactions 
occurring  in  the  presence  of  a  ferment.  Until  we  know  whether 
the  antiferment  produces  its  effects  by  combining  with  the 
ferment  (either  chemically  or  mechanically)  or  by  decreasing 
directly  the  velocity  of  the  chemical  reaction,  the  classifica- 
tion cannot  be  made.  Only  in  case  the  latter  of  these  two 
possibilities  were  proved  to  be  the  correct  one  could  we 
look  upon  the  antiferments  as  negative  catalyzers. 


FERMENTS  AND   FERMENTATION.  81 

The  catalytic  agents  produced  in  living  cells  or  tissues  are 
called  ferments.  They  are  usually  divided  into  two  groups, 
the  so-called  organized  and  u?iorga?iizcd  ferments.  The  first 
term  is  applied  to  those  ferments  which  are  connected  in  some 
way  with  the  life  of  the  cells  in  which  they  are  produced, 
and  which  cannot  be  extracted  from  these  cells.  The  un- 
organized ferments  can,  on  the  other  hand,  be  extracted 
from  the  cells  in  which  they  are  formed,  and  are  able  to 
produce  their  characteristic  actions  outside  of  the  cells  as 
well.  The  unorganized  ferments  are  also  known  as  enzymes 
(Kuhne).  To  the  latter  class  belong  all  the  digestive  ferments, 
amylase,  maltase,  acid-  and  alkali-proteinase,  etc.,  which 
it  has  been  possible  to  extract  from  the  tissues  or  secretions 
of  the  alimentary  tract,  and  which  produce  their  characteristic 
reactions  in  a  test-tube  as  well  as  in  the  living  intestinal 
tract.  To  the  class  of  organized  ferments  belong  all  those 
whose  presence  we  recognize  only  by  their  chemical  be- 
havior and  whose  activities  continue  only  as  long  as  the 
cell  in  which  they  were  produced  is  intact.  Many  of  the 
"vital"  activities  of  tissues  have  to  be  attributed  to  such 
organized  ferments.  It  is  useless  to  enumerate  the  organized 
ferments,  because  the  list  of  unorganized  ferments  (enzymes) 
is  constantly  growing  at  the  expense  of  the  organized,  and  we 
may  hope  in  time  to  speak  of  enzymes  alone.  To  illustrate, 
we  need  only  cite  Buchner's  successful  extraction  of  zymase 
from  the  yeast-cell,  which  is  able  to  bring  about  the  decom- 
position of  glucose  into  alcohol  and  carbon  dioxide  quite  as 
readily  as  the  yeast-cell  itself.  The  discovery  of  Buchner  is 
mentioned  in  this  connection  because  it  takes  away  one  of 
the  pillars  which  for  decades  have  been  utilized  to  support 
the  idea  of  the  essential  difference  between  organized  and  un- 
organized ferments.  In  the  pages  which  follow  the  terms 
ferment  and  enzyme  are  used  synonymously. 

The  number  of  known  ferments  is  already  very  large,  and 
is  being  added  to  daily.  It  is  unfortunate  that  a  uniform 
system  of  nomenclature  has  not  yet  been  adopted  by  all  the 


82  PHYSIOLOGY  OF  ALIMENTATION. 

workers  in  this  field.  Persistence  in  the  use  of  old  methods 
of  naming  even  newly  discovered  enzymes,  and  the  existence 
of  the  same  ferment  under  different  names,  are  extremely 
confusing.  The  best  method  of  naming  ferments  to-day 
is  to  add  the  ending  ase  to  the  root  of  the  Latin  or  Greek  name 
of  the  substance  upon  which  the  ferment  acts.  Thus  maltase 
acts  on  maltose,  sucrase  on  sucrose,  tyrosinase  on  tyrosin, 
amylase  on  starch,  etc.  Since  the  action  of  many,  probably 
all,  ferments  is  reversible  (as  will  be  explained  later),  and  as 
in  this  way  several  names  might  be  given  to  one  and  the 
same  ferment,  it  should  be  the  rule  to  add  the  ending  ase 
to  the  root  of  the  chemically  more  complex  substance  upon 
which  the  ferment  acts.  The  ferment  which  accelerates  the 
decomposition  of  sucrose  into  "  invert-sugar "  is  therefore 
better  named  sucrase  than  invertase,  for  sucrose  is  chem- 
ically more  complex  than  the  dextrose  or  the  lsevulose  which 
constitute  the  invert-sugar.  It  is  sometimes  convenient  to 
add  the  ending  ase  to  the  Latin  or  Greek  root  of  a  word  express- 
ive of  some  striking  characteristic  of  a  group  of  ferments. 
Under  the  oxidases,  for  instance,  are  classed  a  large  number 
of  individual  enzymes,  all  of  which  have  the  power  of  catalyz- 
ing the  oxidation  of  various  chemical  substances.  But  there 
are  many  specific  oxidases,  and  these  are  regrouped  under 
the  general  heading,  according  to  the  substance  or  sub- 
stances with  the  oxidation  of  which  they  are  particularly 
concerned,  as  tyrosinase,  laccase,  olease,  etc. 

Sometimes  ferments  having  the  same  specific  activity 
show  differences  in  their  behavior  toward  altered  external 
conditions.  For  example,  the  lipase  (steapsin)  obtained 
from  the  pancreas  does  not  behave  in  exactly  the  same  way 
toward  changes  in  temperature  and  concentration,  toward 
acids,  alkalies,  etc.,  as  the  lipase  obtained  from  certain  vege- 
table cells.  This  has  aroused  the  suspicion  that  they  may  not 
all  be  identical.  For  this  reason  ferments  are  often  spoken 
of  in  the  plural,  as  lipases,  meaning  thereby  fat-splitting 
enzymes  derived  from  any  source. 


FERMENTS   AND  FERMENTATION.  W 

We  arc  only  jusi  beginning  to  gel  some  idea  of  I  be  chemical 
composition  of  a  few  of  the  simpler  ferments.  For  this 
reason  the  recognition  of  the  existence  of  a  ferment  within 
a  cell  or  out  of  it  is  Still  dependent,  not  upon  the  recognition 
of  the  chemical  substance  itself,  but  rather  upon  the  dis- 
covery of  certain  properties  common  to  all  ferments  and 
specific  ones  characteristic  of  separate  enzymes.  The  fol- 
lowing are  usually  looked  upon  as  properties  common  to  all 
ferments,  and  the  first  four  are  utilized  in  proving  the  existence 
of  a  ferment  in  cells  or  tissues,  or  in  extracts  made  of  these. 

(a)  A  ferment  does  not  initiate  a  chemical  reaction  but  only 
alters  its  velocity.  The  ferment  acts  essentially  through  con- 
tact, in  that  its  mere  presence  is  responsible  for  the  altered 
velocity  of  the  catalyzed  reaction.  At  the  end  of  the  reaction 
the  ferment  is  (under  ordinary  circumstances)  found  in  an 
unaltered  state  in  the  reaction  mixture.  The  ferment  does 
not,  therefore,  enter  into  the  end-products  of  the  reaction. 
When  hydrochloric  acid  is  poured  upon  sodium  carbonate  in 
order  to  decompose  it,  we  have  at  the  end  of  the  reaction  the 
chlorine  of  the  hydrochloric  acid  appearing  in  the  sodium 
chloride,  and  the  hydrogen  in  the  carbonic  acid.  Not  so,  how- 
ever, in  the  case  of  a  ferment.  When  sucrase  (invertase, 
invertin)  acts  upon  cane-sugar,  dextrose  and  laevulose  are 
formed,  but  neither  of  these  products  contains  in  chemical 
combination  any  part  or  all  of  the  sucrase  molecule, — the 
sucrase  is  found  in  an  unaltered  condition  at  the  end  of  the 
reaction. 

It  is  possible  that  the  molecules  of  the  ferment  enter  tem- 
porarily into  chemical  combination  with  the  substance  acted 
upon  or  with  its  products.  This  assumption  is  made  on  the 
ground  that  in'  some  simple  catalytic  processes  the  catalyzer 
does  temporarily  combine  with  the  reacting  substances.  This 
is  t  he  case,  for  example,  in  the  manufacture  of  sulphuric  acid, 
in  which  steam,  sulphur  dioxide,  oxygen,  and  nitrogen  dioxide 
are  introduced  simultaneously  into  a  large  chamber.  In 
brief,  it  is  believed  that  the  sulphur  dioxide  and  steam  com- 


84  PHYSIOLOGY  OF  ALIMENTATION. 

bine  to  form  sulphurous  acid,  which  is  oxidized  to  sulphuric 
by  the  nitrogen  tetroxide  formed  through  the  union  of  the 
nitrogen  dioxide  with  oxygen.  The  nitrogen  dioxide,  which 
plays  the  role  of  a  catalyzer  in  this  reaction,  unites  first  of  all 
with  oxygen  to  form  nitrogen  tetroxide,  but  the  nitrogen 
dioxide  is  restored  immediately  in  that  the  sulphurous  acid 
takes  away  the  oxygen  from  the  nitrogen  tetroxide.  The 
nitrogen  dioxide  acts,  therefore,  only  through  its  mere  pres- 
ence, appearing  in  an  unaltered  state  at  the  end  of  the  reac- 
tion. Nor  does  it  initiate  a  chemical  reaction,  for  the  oxida- 
tion to  sulphuric  acid  occurs  whenever  sulphurous  acid  is 
exposed  to  oxygen.  But  the  reaction,  which  under  these 
circumstances  occurs  only  very  slowly,  occurs  very  rapidly 
when  nitrogen  dioxide  is  present. 

There  are  other  facts,  into  a  discussion  of  which  we  cannot 
go  here,  that  speak  against  this  conception  of  the  action  of  a 
ferment,  and  seem  to  indicate  that  certain  physical  charac- 
teristics of  the  ferment  (or,  in  general,  any  catalytic  agent), 
such  as  its  surface,  electrical  condition,  etc.,  constitute  the 
real  cause  of  its  peculiar  action.  However  this  problem  may 
ultimately  be  settled,  the  fact  seems  fairly  well  established 
that,  except  for  a  simple  decomposition  which  is  to  be  dis- 
cussed later,  the  ferment  appears  in  an  unaltered  state  at  the 
end  of  the  reaction. 

(6)  In  infinite  time  the  amount  of  chemical  change  brought 
about  by  a  ferment  is  independent  of  the  concentration  of  the 
ferment.  This  means  that  a  small  amount  of  a  ferment  will 
bring  about  as  much  chemical  change  as  a  larger  one,  pro- 
vided unlimited  time  is  given.  In  this  regard,  therefore,  a 
ferment  differs  from  the  ordinary  constituent  of  a  reaction 
mixture.  We  know  from  the  law  of  chemical  mass-action  of 
Guldberg  and  Waage  that  in  any  ordinary  chemical  reaction 
the  amount  of  the  chemical  change  is  proportional  to  the 
concentration  of  the  reacting  substances.  This  does  not  hold 
in  the  case  of  ferments,  where  the  amount  of  ferment  is  in 
nearly  all  cases  exceedingly  small  when  compared  with  the 


FERMENTS   AND   FERMENTATION.  85 

amount  of  substance  acted  upon.  This  fact  alone  speaks 
against  any  idea  that  fermentation  is  dependent  upon  a 
quantitative  chemical  decomposition  between  catalyzer  and 
catalyzed  substance — that,  in  other  words,  we  are  dealing 
with  a  stoichiometrical  reaction. 

It  is  well  to  note  that  what  has  been  said  holds  true  only 
when  infinite  time  is  allowed.  For  shorter  periods — which 
vary  with  the  nature  of  the  catalyzer  and  the  nature  of  the 
substance  or  substances  catalyzed — the  degree  of  fermentation 
is  clearly  and  often  definitely  a  function  of  the  concentration  of 
the  ferment.  We  cannot  here  enter  into  a  discussion  of  the 
influence  of  the  concentration  of  a  ferment  upon  the  velocity 
of  the  fermentation.  In  general  it  can  be  said  that  only 
within  exceedingly  narrow  limits  of  time  and  concentration, 
both  of  the  substances  undergoing  catalysis  and  the  catalyzer, 
is  the  rate  of  fermentation  approximately  directly  propor- 
tional to  the  concentration  of  the  ferment.  In  the  majority 
of  instances  the  variation  is  very  great,  and  an  increase  in  the 
concentration  of  the  ferment  is  not  followed  by  a  correspond- 
ing increase  in  the  rate  of  the  fermentation.  Thus  doubling 
the  concentration  of  a  ferment  in  a  certain  reaction  mixture 
does  not  multiply  the  rate  of  the  catalysis  by  two,  but  by  less 
than  two. 

The  reason  why  the  rate  of  catalysis  is  not  proportional 
to  the  amount  of  ferment  added  is  not  yet  entirely  clear. 
It  seems  to  be  dependent,  in  part  at  least,  upon  a  decom- 
position which  the  ferment  itself  suffers,  in  consequence  of 
which  its  concentration  is  steadily  decreased.  More  potent 
than  thia  seems  to  be  the  accumulation  of  the  products  of 
the  fermentation.  The  opinion  has  been  expressed  that 
the  accumulation  of  the  products  of  the  catalyzed  reaction 
injures  the  ferment,  but  this  view  can  no  longer  be  held, 
since  we  have  learned  that  the  activity  of  many  enzymes 
is  reversible.  For  example,  in  the  action  of  maltase  on 
maltose  and  the  production  of  dextrose  we  might  assume 


86  PHYSIOLOGY  OF  ALIMENTATION. 

that  the  ever-increasing  amount  of  glucose  in  the  reaction 
mixture  interferes  with  the  further  action  of  the  maltase. 
The  argument  falls  to  the  ground,  however,  when  we  deal 
with  the  action  of  maltase  on  glucose  and  the  production 
of  maltose.  If  glucose  interfered  with  the  action  of  the 
enzyme,  the  velocity  of  this  reaction  ought  to  be  lowest 
at  first  and  increase  as  more  and  more  maltose  is  produced. 
As  an  actual  matter  of  fact,  the  opposite  occurs,  and  the 
velocity  of  the  reaction  becomes  progressively  less  as  the 
maltose  accumulates.  In  either  case,  therefore,  the  accu- 
mulation of  the  fermentation-products  seems  to  interfere 
with  the  chemical  reaction  itself. 

(c)  Ferments  are  usually  characterized  by  a  great  sensi- 
tiveness to  comparatively  low  temperatures.  In  fact,  it  is  one 
of  the  commonest  means  employed  in  proving  that  a  cer- 
tain chemical  reaction  is  dependent  upon  the  presence  of  a 
ferment,  to  heat  the  reaction  mixture  to  boiling  and  find 
that  after  this  treatment  the  reaction  no  longer  takes  place. 
(In  most  instances  the  reaction  does  in  reality  still  occur, 
only  so  infinitely  slowly,  as  a  general  thing,  that  it  is  unrecog- 
nizable by  the  analytical  methods  at  our  disposal.)  This 
means  that  a  temperature  of  100°  C.  destroys  the  activity 
of  the  ferment.  Some  few  ferments  are  able  to  endure 
this  temperature  or  even  a  higher  one  for  a  short  time,  but 
the  vast  majority  cannot  stand  heating  to  even  60°  C.  for 
any  length  of  time.  The  cause  of  this  inactivation  of  the 
ferment  is  to  be  sought  in  a  decomposition  which  it  under- 
goes. The  nature  of  this  decomposition  is  not  as  yet  under- 
stood. Ferments  are  not  nearly  so  sensitive  to  tempera- 
ture in  the  dry  state  as  in  the  moist.  Many  ferments  which 
are  readily  destroyed  by  heating  to  60°  C.  for  some  minutes 
in  the  presence  of  water  withstand  a  temperature  of  120°  C. 
for  much  longer  periods  if  the  ferments  are  thoroughly 
dry.  An  every-day  illustration  of  this  is  found  in  the  well* 
known  fact  that  in  surgical  sterilization  the  death  of  all 
bacteria  and  spores  is  obtained  much  more  easily  by  the 


FERMENTS  AND   FERMENTATION.  $t 

use  of  moist  heat  than  dry  heat.  These  facts  seem  to  indi- 
cate that  the  decomposition  of  the  ferment  is  accompli 
through  the  taking  up  of  water— in  other  words,  that  we 
are  dealing  with  a  hydrolysis  of  the  ferment.  The  pos- 
sibility of  a  mere  change  in  the  physical  stale  ol  the  fer- 
ment as  the  cause  of  its  inactivation  through  heat  must, 
however,  also  be  considered,  for  there  are  many  reasons  at 
hand  for  believing  that  ferments  owe  their  specific  virtues 
quite  as  much  to  their  physical  state  of  aggregation  as  to 
their  chemical  make-up. 

The  fact  that  ferments  suffer  a  decomposition  when 
exposed  to  higher  temperatures  explains  the  peculiar  be- 
havior of  chemical  reactions  which  are  being  catalyzed 
by  ferments  when  the  reaction  mixtures  are  exposed  to 
various  temperatures.  As  is  well  known,  the  velocity  of 
ordinary  chemical  reactions  varies  greatly  with  different 
temperatures.  An  every-day  illustration  of  this  fact  is 
found  in  the  use  of  heat  to  hasten  chemical  decomposi- 
tion in  our  ordinary  analytical  reactions,  and  the  resort  to 
refrigeration  in  the  effort  to  delay  decomposition  in  animal 
and  vegetable  matter.  For  ordinary  chemical  reactions  it 
has  been  found  that  the  reaction  velocity  is,  roughly  speak- 
ing, doubled  or  trebled  for  every  increase  of  10°  C.  in  tem- 
perature.1 When  we  are  dealing  with  chemical  reactions 
which  are  taking  place  under  the  influence  of  a  ferment, 
things  are  entirely  different.  Within  certain  limits  we 
have  here  also  an  increase  in  reaction  velocity  with  an  in- 
crease in  temperature,  but  when  a  certain  point  is  reached — 
which  varies  with  different  ferments,  and  with  the  same 
ferment  acting  in  different  media — the  reaction  velocity 
no  longer  increases  but  decreases  with  a  further  elevation 
of  the  temperature.  Finally  a  point  is  reached  at  which 
the   reaction   ceases   entirely    (apparently).     It    is    for    this 

1  Cohen:  Physical  Chemistry  for  Physicians.  Translated  by  Mai-hx 
11.  Fischer,  New  York,  1903,  p.  53. 


88  PHYSIOLOGY  OF  ALIMENTATION. 

reason  that  an  optimum  temperature  exists  in  the  case  of 
all  ferments.  By  this  is  meant  the  temperature  at  which 
the  particular  ferment  under  the  given  conditions  brings 
about  its  characteristic  effects  most  rapidly — that  is  to  say, 
its  reaction  velocity  is  greatest.  This  optimum  tempera- 
ture lies,  for  most  ferments,  close  to  40°  C. 

The  reason  for  the  existence  of  such  a  maximal  reaction 
velocity  can  be  readily  understood  from  what  has  been 
said  before.  If  the  ferment  remained  unchanged  upon 
heating  a  reaction  mixture,  the  velocity  of  the  chemical 
reaction  would  increase  progressively  with  an  increase  in 
temperature,  just  as  in  any  ordinary  reaction  mixture.  When, 
however,  we  are  dealing  with  reactions  in  which  ferments 
are  concerned,  the  ferment  is  all  the  time  undergoing  a 
decomposition  itself,  and  the  rate  of  this  decomposition  is 
also  a  function  of  the  temperature.  It  is  known,  in  general, 
that  the  length  of  time  required  to  destroy  a  ferment  at  a 
comparatively  low  temperature  is  greatly  reduced  by  an 
elevation  of  only  a  few  degrees  centigrade.  Tammann,  who 
has  worked  out  the  velocity  of  the  decomposition  of  the 
ferment  synaptase  (emulsin)  above  60°  C,  finds  that  an 
increase  in  temperature  of  10°  C.  multiplies  the  decom- 
position velocity  of  the  ferment  by  more  than  seven.  In  a 
reaction  mixture  in  which  a  ferment  is  concerned  we  have 
therefore  at  least  two  reactions  going  on  side  by  side,  and 
it  is  the  product  of  these  two  simultaneously  occurring 
reactions  which  is  represented  by  a  curve  that  attains  a 
maximum  at  one  point.  Since  the  two  reactions  which  yield 
this  curve  have  their  individual  characteristics,  it  can  be 
readily  understood  why  the  curves  not  only  of  different 
enzymes,  but  even  of  the  same  enzyme  acting  under  different 
external  conditions,  must  vary.  In  Fig.  18  are  shown  the 
curves  representing  graphically  the  changing  reaction  veloc- 
ities of  various  ferments  with  variations  in  the  temperature. 
Curves  1,  2,  3,  and  4  illustrate  the  behavior  of  indigo  enzyme 
obtained  from  various  sources;    carve  5  that  of  synaptase 


FERMENTS   AND   I- Eli  MENTATION. 


v.. 


(emulsin)  obtained  from  sweet  almonds.  The  curves  show 
very  well  a  region  in  which  an  increase  in  temperature  is 
followed  by  an  increase  in  the  rate  of  chemical  reaction,  the 
attainment  of  an  optimum,  and  the  rapid  fall  to  the  base- 
line, with  only  a  slight  further  increase  in  the  temperature 
beyond  the  optimum.  In  general,  it  may  be  said  that  all 
ferments  behave  in  a  similar  manner.1 


V/ 

7 

3^- 

\ 

^^ 

5 

\ 

>-^~ 

II 


10 


80 


90 


20  30         -JO  50         60  70 

TEMPERATURE  IN   DEGREES  CENTIGRADE 

Fig.  IS. 

(Copied  from  Cohen:  Physical  Chemistry  for  Physicians.     Trans,  by 

Fischer,  New  York,  1903,  p.  56.) 

(d)  The  reactions  which  are  catalyzed  by  a  ferrm  nt  are 
rarely,  if  ever,  complete  unless  the  products  of  the  reaction  arc 
removed  as  soon  as  formed.  By  this  is  meant  that  if  a  certain 
substance  and  a  ferment  capable  of  acting  upon  this  sub- 
stance are  mixed  together,  say  in  a  test-tube,  not  all  of  the 
substance  will  bo  acted  upon  by  the  ferment,  but  when  the 


1  Cohen:  Physical  Chemistry  for  Physicians.     Translated  by  Martin 
H.  Fischer,  New  York,  L903,  p.  55. 


90  PHYSIOLOGY  OF  ALIMENTATION. 

reaction  has  come  to  a  standstill  a  certain  amount  of  the 
substance  will  be  found  unchanged  in  the  reaction  mixture. 
If,  for  example,  a  certain  amount  of  fat  and  lipase  (steapsin) 
are  mixed  together  and  the  whole  is  allowed  to  stand  until 
the  reaction  has  come  to  a  standstill,  it  is  found  that  some 
of  the  fat  has  been  left  in  an  undigested  state.  What  has 
been  said  of  fat  holds  true  also  for  a  large  number  of  other 
ferments — in  fact,  all  that  have  thus  far  been  investigated. 

It  is  only  recently  that  an  explanation  of  this  interesting 
and  fundamental  fact  has  been  given,  and,  as  will  become 
apparent  later,  a  large  number  of  physiological  processes 
rendered  more  intelligible  in  consequence.  It  used  to  be 
said  that  the  products  of  the  fermentation  interfered  with 
its  further  progress.  We  know  now,  however,  that  the  reason 
for  the  incompleteness  of  the  chemical  reaction  lies  in  the 
fact  that  the  ferment  is  continually  re-forming  from  the 
products  of  the  reaction  the  substance  or  substances  with  which 
the  ferment  was  mixed  originally.  Thus,  in  the  case  of  fat, 
which  is  split  into  fatty  acid  and  alcohol  by  lipase,  we 
have  two  reactions  going  on  side  by  side:  first,  the  long- 
recognized  analytical  one,  by  which  fatty  acid  and  alcohol 
are  formed  from  the  fat;  and,  second,  a  synthetical  one,  by 
which  fat  is  formed  from  the  fatty  acid  and  alcohol.  Both 
reactions  are  catalyzed  by  the  same  ferment,  the  action  of 
which  we  say  is  reversible.  This  reversibility  of  the  action  of 
a  ferment  is  another  of  its  fundamental  characteristics.  Whether 
in  any  given  case  a  ferment  acts  synthetically  or  analytically, 
it  will  be  shown  later,  is  determined  solely  by  the  ordinary 
laws  of  chemical  equilibrium. 

If  the  products  of  a  chemical  reaction  which  is  being  catalyzed 
by  a  ferment  are  removed  as  soon  as  formed,  the  reaction 
will  be  completed.  If,  in  the  illustration  cited  above,  the 
fat  and  lipase  are  put,  not  into  a  test-tube,  but  into  a  parch- 
ment bag  suspended  in  a  current  of  water,  all  the  fat  will 
be  split  into  fatty  acid  and  alcohol.  Under  these  circum- 
stances the  fatty  acid  and  alcohol  diffuse  through  the  parch- 


FERMENTS  AND   FERMENTATION.  91 

merit  wall  as  soon  as  formed  and  are  carried  off  by  the 
stream  of  water.    The  products  cannot  therefore  accumulate 

and  be  synthesized  into  fat.     In    this  way  all    the    fat    is 
ultimately  split  into  fatty  acid  and  alcohol. 

(r)  For  reasons  which  arc  at  present  not  well  under- 
stood, the  fermentative  activity  of  extracts  of  organs  or  the  isolated 
ferments  of  the  alimentary  secretions  is  disappointingly  low 
irli en  compared  tvith  the  activity  of  the  uninjured  organ  or  the 
freshly  oldained  secretion.  The  fact  that  all  the  ferments 
1 1  his  far  studied  are  apparently  colloidal  in  character,  and 
consequently  exceedingly  sensitive  to  changes  in  their  sur- 
roundings, is  perhaps  responsible  for  this,  at  least  in  part. 
Some  very  active  preparations  of  ferments  have,  however, 
been  described.  The  most  active  are,  no  doubt,  the  prepara- 
tions of  amylase  prepared  by  Weinland.1  The  following  two 
experiments,  taken  from  his  note-books,  may  serve  as  illus- 
trations. 

(a)  Forty-one  grams  of  the  mixed  pancreas  from  three  pigs 
are  ground  up  for  ten  minutes  in  a  mortar  with  41  grams  of 
quartz  sand.  To  the  mixture  are  added  21  grams  of  infusorial 
earth,  and  the  whole  is  ground  for  another  ten  minutes.  A 
paste  results.  This  paste  is  placed  in  a  cloth  and  subjected  to 
the  pressure  of  a  Btjchxer  press.  Only  7  c.c.  of  juice  (1)  are 
obtained.  On  the  following  day  the  paste  is  mixed  with 
30  c.c.  of  0.9  percent  NaCl  solution  and  10  c.c.  of  disodium 
phosphate  solution.  This  gives  a  somewhat  thin  mixture. 
This  is  again  put  under  the  press  and  29  c.c.  of  juice  are  ob- 
tained, to  which  are  added  the  7  c.c.  (1)  obtained  before.  A 
third  pressing  raises  the  entire  amount  of  extract  to  43  c.c. 
(in  other  words,  about  the  volume  of  the  original  amount  of 
pancreas).  The  extract  is  filtered,  when  a  clear,  yellowish 
solution  results,  and  this  is  covered  with  toluol  to  prevent 
the  development  of  bacteria.  Five  days  later  5  c.c.  iA'  a  two- 
percent  glycogen  solution  (upon  which  amylase  acts  :is  readily 
as  upon  starch)  are  mixed  at  room  temperature  with  a  little 

KI-I     solution,    when    the   whole   assumes    a    dark-red    color. 

indicating  the  presence  of  the  glycogen.     To  this  mixture  there 
1  Wkixi  wi>:  Personally  communicated. 


92  PHYSIOLOGY  OF  ALIMENTATION. 

is  added  0.1  c.c.  of  the  extract  prepared  above.  In  one 
minute  the  glycogen  solution  has  lost  its  color,  and  the  Trommer 
test  results  positively.  The  paste  from  which  the  extract  has 
been  obtained  fails  to  remove  the  color  from  a  similarly  pre- 
pared mixture  of  glycogen  and  iodine,  even  when  several 
minutes  are  allowed. 

(/?)  By  methods  similar  to  those  described  above,  60  c.c. 
of  juice  are  obtained  from  59.4  grams  of  dogs'  pancreas.  The 
extract  has  been  kept  for  five  days  under  toluol.  When  2  c.c. 
of  this  extract  are  mixed  at  room  temperature  with  1  c.c.  of 
a  two-percent  glycogen  solution,  and  to  this  is  added  as 
quickly  as  possible  a  KI-I  solution,  no  change  in  color  is  ob- 
tained, indicating  that  the  glycogen  has  been  changed  into 
sugar  even  in  these  few  seconds.  Even  when  3  c.c.  of  the 
glycogen  solution  are  added  to  the  extract,  the  decomposition 
of  the  glycogen  occurs  so  quickly  that  a  reaction  with  iodine 
cannot  be  obtained.  Not  until  3  c.c.  of  the  extract  are  mixed 
with  25  c.c.  of  the  glycogen  solution  (J  gram  dry  glycogen)  is 
this  possible.  After  this  mixture  has  been  kept  in  the  incu- 
bator at  37°  C.  for  one-half  hour,  it,  too,  no  longer  gives  a 
positive  iodine  reaction.  On  the  following  day  0.5  c.c.  of  the 
extract  is  mixed  with  5  c.c.  of  the  glycogen  solution.  After 
standing  for  eight  minutes  at  room  temperature  the  mixture 
has  lost  its  color.  The  Trommer  test  is  positive.  Examina- 
tion of  the  paste  from  which  the  extract  has  been  obtained 
shows  it  to  be  unable  to  act  upon  the  glycogen. 

(/)  It  seems  to  be  true  of  a  number  of  the  ferments  found 
in  cells  and  in  their  secretions  that  these  ferments  do  not 
exist  as  such  in  them,  but  in  an  inactive  form  known  as 
proferments  or  zymogens.  The  most  striking  example  of  such 
a  zymogen  is  probably  the  entirely  inactive  proferment  of 
trypsin  (trypsinogen,  as  it  is  sometimes  called),  found  in  the 
pancreatic  juice.  This  proferment  (as  present  in  the  pan- 
creatic juice  obtained  directly  from  the  pancreatic  duct)  is 
not  able  to  act  upon  proteins  until  it  has  been  converted 
into  trypsin  (alkali-proteinase)  by  coming  in  contact  with  a 
substance  contained  in  the  secretions  of  the  small  intestine 
(enterokinase).  The  proferment  of  alkali-proteinase  is  found 
also  in  the  body  of  the  pancreas,  and  this  fact  has  been  con- 


FERMENTS   AND    FERMENTATION.  93 

Bidered  in  trying  to  explain  why  the  pancreas  is  not  digested 

by  its  own  trypsin,  or  in  general  why  any  organ  is  not  digest ed 
by  the  ferments  contained  in  it.  This  explanation  of  the 
immunity  of  tissues  against  their  own  ferments  can  hold  in 
only  a  few  cases,  however.  For  other  enzymes  the  existence 
of  proferments  has  not  been  so  definitely  established. 

There  seems  to  be  little  doubt  but  that  proferments  exist 
for  rennin  (caseinase),  steapsin  (lipase),  and  pepsin  (acid- 
proteinase).  The  existence  of  a  proferment  ofacid-proteinase 
in  the  gastric  mucosa  is  demonstrated  by  the  following  facts: 
If  the  minced  mucous  membrane  of  the  stomach  of  an  animal 
is  extracted  with  a  dilute  alkaline  solution  and  the  whole  is  fil- 
tered, a  clear  solution  is  obtained  which  does  notact  on  proteins. 
If  this  solution  is  acidulated  with  hydrochloric  acid  it  digests 
proteins  rapidly.  But  if  this  acid  solution  is  rendered  alka- 
line once  more,  and  is  then  again  acidulated  with  hydro- 
chloric acid,  the  digestive  properties  of  the  solution  for  pro- 
teins will  have  been  lost.  These  experimental  facts  are 
explained  on  the  assumption  that  pepsin  is  readily  destroyed 
in  an  alkaline  medium,  while  its  zymogen  is  not,  and  that  the 
conversion  of  the  zymogen  into  the  ferment  is  accomplished 
through  the  acid. 

The  relation  that  ferments  bear  to  their  proferments  is 
not  understood.  The  conversion  of  the  proferment  into 
the  ferment  may  at  times  be  accomplished  through  the 
action  of  a  specific  substance,  such  as  enterokinase.  But 
the  character  of  this  substance,  which  by  some  is  regarded 
as  itself  a  ferment  (whence  the  name),  by  others  as  a  sub- 
stance differing  markedly  from  this  group  of  compounds, 
is  also  not  understood.  In  the  majority  of  instances  dilute 
acids  are  able  to  bring  about  a  conversion  of  the  proferment 
into  the  ferment.  Whether  this  represents  more  than  a 
simple  change  in  the  physical  state  of  a  colloid  is  still  un- 
known. 

2.  Inorganic  Ferments. — Beyond  what  has  already  been 
said  we  cannot  here  enter  into  a   discussion  of  the  various 


94  PHYSIOLOGY  OF  ALIMENTATION. 

theories  of  fermentation  which  have  been  proposed  from 
time  to  time.  Within  the  last  few  years,  however,  the  work 
which  has  been  done  on  the  so-called  inorganic  ferments 
has  so  altered  our  older  conceptions  of  the  essential  nature 
of  fermentation  that  a  discussion  of  some  of  the  analogies 
between  the  organic  and  inorganic  ferments  may  not  be 
amiss,  even  though  the  facts  as  they  stand  now  have  a 
greater  bearing  on  the  theoretical  than  on  the  practical 
side  of  the  medical  problems  of  fermentation. 

As  early  as  1863  Schonbein  pointed  out  the  analogy  which 
exists  between  the  influence  of  finely  divided  metals  (such 
as  platinum,  iridium,  silver)  and  that  of  a  number  of  ferments 
on  the  velocity  of  certain  chemical  reactions.  The  decom- 
position of  hydrogen  peroxide,  for  instance,  is  accelerated 
not  only  by  the  addition  of  aqueous  extracts  of  various 
animal  and  vegetable  cells  which  contain  ferments,  but 
also  through  the  addition  of  the  finely  divided  noble  metals 
mentioned  above.  The  decomposition  of  hydrogen  peroxide 
occurs  also  in  the  absence  of  these  substances,  only  then 
much  more  slowly,  so  that  the  finely  divided  metals  possess 
the  characteristic  property  of  a  ferment,  namely,  that  of 
altering  the  velocity  of  a  reaction  which  occurs  in  its  absence 
also. 

Through  the  more  recent  work  of  Bredig  and  with  him 
von  Berneck,  Reinders,  Ikeda,  and  the  efforts  of  McIntosh, 
Billitzer,  Neilson,  and  others,  our  knowledge  of  the  inor- 
ganic ferments  has  been  greatly  increased.  For  a  fuller 
account  than  can  be  given  here  and  for  references  to  the 
literature  the  reader  is  referred  to  the  monograph  of  Bredig.1 

In  place  of  the  coarsely  powdered  metals  employed  by 
the  older  observers,  Bredig  used  so-called  colloidal  or  pseudo- 
solutions  of  these  metals.  The  solutions  are  prepared  by 
sending  an  electric  current  through  electrodes  of  the  noble 

1  Bredig:  Anorganische  Fermente,  Leipzig.  1901;  Ergebnisse  d. 
Physiologie,  1902, 1,  lte  Abth.,  p.  134. 


FERMENTS   AND   FERMENTATION.  95 

metals  while  these  are  held  in  a  large  dish  of  absolutely 
pure  water,  The  metal  emanates  in  a  cloud  from  one  of 
the  electrodes  and  remains  suspended  in  the  liquid.  The 
colloidal  solution  is  therefore  not  a  true  solution,  but  rather 
a  suspension  of  very  fine  particles.  The  coarser  particles 
are  filtered  off,  and  the  sol  (a  term  applied  to  a  colloid  in 
the  liquid  state)  which  remains  behind  shows  properties 
exceedingly  like  those  of  the  ordinary  ferments.  For  this 
reason  these  sols  have  been  called  inorganic  ferments  by 
Bredig.  Depending  upon  the  metal  from  which  the  sol 
is  prepared,  we  speak  of  platinumsol,  goldsol,  etc. 

A  large  number  of  ferments  from  different  sources  have  the 
power  of  catalyzing  the  decomposition  of  hydrogen  peroxide 
into  water  and  oxygen.  Colloidal  solutions  of  platinum 
have  the  same  power.  Interestingly  enough,  as  is  the  case 
with  the  true  ferments,  this  inorganic  ferment  also  is  active 
in  exceedingly  small  quantities.  Thus  one  gram-atom  of 
platinum  (194.8  grams)  diluted  with  seventy  million  liters 
of  water  is  still  able  to  accelerate  the  decomposition  of 
more  than  a  million  times  its  amount  of  hydrogen  peroxide. 
One  cubic  centimeter  of  the  solution  which  still  shows 
"fermentative"  properties  therefore  contains  only  1/300000 
milligram  of  platinum.  It  would  be  difficult  to  rival  this 
with  figures  taken  from  any  of  the  organic  ferments. 

The  rapidity  of  the  decomposition  of  hydrogen  peroxide 
by  platinumsol  is  dependent  upon  the  concentration  of  the 
platinum,  just  as  in  the  case  of  a  true  ferment.  If  infinite 
time  is  allowed,  a  small  amount  of  platinumsol  will  bring  about 
as  much  decomposition  as  a  larger  amount.  In  shorter  periods 
the  velocity  of  the  catalysis  is  definitely  dependent  upon 
the  concentration  of  the  colloidal  platinum,  very  much 
as  in  the  case  of  the  ordinary  ferments  which  have  the 
power  of  catalyzing  the  decomposition  of  hydrogen  peroxide. 

Even  though  not  sensitive  to  the  same  degree  as  organic  fer- 
ments, the  inorganic  ferments  are  exceedingly  sensitive  to  heat. 
In  the  preparation  of  the  sols  great  care  has  to  be  exercised  to 


96  PHYSIOLOGY  OF  ALIMENTATION. 

prevent  overheating  of  the  water,  as  this  causes  the  platinum, 
gold,  silver,  or  whatever  metal  is  being  employed,  to  be 
precipitated.  In  other  words,  the  inorganic  ferment  is 
destroyed.  For  this  reason,  therefore,  the  dish  of  water 
in  which  the  colloidal  solution  is  being  prepared  is  kept 
cooled  with  ice,  and  overheating  by  allowing  the  electric 
current  to  pass  through  the  water  for  too  long  a  time  is 
carefully  avoided.  It  was  pointed  out  above  that  the  de- 
composition of  the  true  ferments  by  heat  might  represent 
nothing  but  a  physical  change.  For,  as  far  as  we  know  now, 
the  organic  ferments  are  all  colloidal  solutions,  and  in  con- 
sequence exceedingly  liable  to  precipitation  (and  inactiva- 
tion)  through  heat.  The  greater  sensitiveness  to  heat  in  the 
case  of  the  true  ferments  is  readily  explained  on  the  ground 
that  these  are  always  impure — mixed  with  salts,  etc.,  from 
which  it  is  impossible  to  free  them — and  consequently  more 
readily  precipitated.  As  will  be  shown  in  greater  detail 
further  on,  the  presence  of  certain  impurities,  such  as  gases 
and  salts,  in  the  colloidal  solutions  of  platinum  greatly 
decreases  their  stability  also.  Colloidal  solutions  of  platinum, 
gold,  etc.,  are  the  more  readily  precipitated  (destroyed)  by 
heat  the  greater  the  amount  of  these  impurities.  It  may 
be  for  this  reason  that  the  purest  ferments  which  have  thus 
far  been  obtained  are  least  sensitive  to  temperature.  Whether 
inorganic  ferments  have  an  optimal  temperature  as  do  the 
true  ferments  is  not  yet  worked  out  sufficiently.  The  recent 
work  of  Ernst  x  shows  that  such  a  temperature  exists  in 
the  case  of  the  decomposition  of  oxyhydrogen  gas  in  aqueous 
solution  in  the  presence  of  colloidal  platinum. 

It  was  held  for  a  long  time  that  the  inorganic  ferments 
differed  from  the  organic  in  one  essential  detail.  While  the 
action  of  the  ordinary  ferment  comes  to  a  standstill  after  a 
certain  time,  a  reaction  catalyzed  by  an  inorganic  ferment 
seemed   always  to  be  complete.     It  was  shown  above  that 

1  Ernst:  Zeitschr.  f.  physik.  Chera.,  1901,  XXXVII,  p.  448. 


FERMENTS   AND   FEh'M E.\  TATION.  97 

the  explanation  of  this   partial   decomposition   by   organic 
ferments  lay  in   the  fad    that  their  action   was  reversible, 

that   they  synthesized  from   the    products  of  the  decompo- 
sition   the   substance  which    was    being   analyzed.     Now    it 
has  been  shown  by  Neilson  '  that  finely  divided  platinum 
is  able  not  only  to  hasten  the  splitting  of  ethyl  butyrate  into 
ethyl  alcohol  and  butyric  acid,  but  is  also  able  to  synthesize 
ethyl  butyrate  from  ethyl  alcohol  and  butyric  acid.    Reversi- 
bility is  therefore  a  characteristic  of  these  inorganic  ferments 
also.2    The  failure  of  the  older  observers  to  discover  that  the 
reactions  catalyzed  by  the  metallic  colloids  are  incomplete 
is  to  be  explained  by  the  character  of  the  reactions  which 
they  studied.     In   the   catalysis  of   hydrogen  peroxide,  for 
example,  by  platinumsol,  one  of  the  products  of  the  decom- 
position— the  oxygen — is  allowed  to  escape  as  soon  as  liberated, 
so  that  even  if  water  could  be  oxidized  to  hydrogen  peroxide 
it  would  not  occur  under  the  conditions  of  the  experiment. 
For,  in   order   that   reversion   may  occur,  all   the  products 
of  the  decomposition  must  be  allowed  to  accumulate.     If 
the  products  of  a  chemical  reaction  catalyzed  by  any  fer- 
ment are  removed  as  fast  as  formed,  that  reaction  is  com- 
plete and  shows  no  "limit." 

A  great  analogy  exists  also  between  the  sensitiveness  of 
the  true  ferments  to  certain  poisons  and  the  sensitiveness 
of  the  colloidal  solutions  of  the  noble  metals  to  these  same 
poisons.  Acids,  bases,  and  salts  affect  different  organic 
ferments  in  different  ways.  The  effect  of  these  same  sub- 
stances upon  the  inorganic  ferments  is  equally  marked. 
The  addition  of  a  mere  trace  of  disodium  phosphate  to  a 
liter  of  colloidal  platinum  solution  caused  an  immediate 
fall  in  the  "velocity  constant"  of  the  decomposition  of 
hydrogen  peroxide  from  0.023  to  0.015.    After  waiting  several 

'Neilson:  Science,  1902,  XV,  p.  715. 

2  The  spongy  platinum  used  by  Neilson  is  no!  a  colloid,  bul  the  nature 
of  its  action  is  no  doubt  the  same  as  that  of  platinumsol. 


98  PHYSIOLOGY   OF  ALIMENTATION. 

days  the  velocity  constant  had  fallen  lower  still — to  0.01 1. 
We  are  familiar  with  this  same  inactivation  in  the  case  of 
the  true  ferments,  and  it  is  not  impossible  that  that  which 
causes  the  platinumsol  to  become  inactive,  namely,  a  pre- 
cipitation of  the  colloidal  par  icles,  lies  at  the  basis  of  the 
inactivation  of  the  true  ferments  also. 

Poisons,  the  action  of  which  upon  organic  ferments  is  more 
or  less  characteristic  and  striking,  show  this  same  action 
when  brought  in  contact  with  inorganic  ferments.  The 
physiological  action  of  hydrocyanic  acid  finds  its  explana- 
tion in  its  power  to  interfere  with  the  oxidizing  ferments 
of  the  cell.  When  added  in  even  exceedingly  minute  traces 
to  oxidizing  (and  other)  ferments  it  reduces  their  action  to  a 
point  where  it  can  scarcely  be  recognized.  The  addition  of 
hydrocyanic  acid  to  platinumsol  reduces  its  action  upon  hydro- 
gen peroxide  in  the  same  striking  way,  for  the  presence  of 
0.0014  milligram  hydrocyanic  acid  in  a  liter  of  the  colloidal 
platinum  solution  reduces  its  action  one-half.  Hydrogen 
sulphide,  which  also  has  a  powerful  action  in  inhibiting  the 
activity  of  organic  ferments,  shows  the  same  behavior  when 
added  to  the  colloidal  solutions  of  the  noble  metals.  The  order 
in  which  the  poisons,  ferments,  and  hydrogen  peroxide  are 
put  together  is  not  without  influence  upon  the  extent  of  the 
inhibition  produced.  The  fact  is  therefore  of  interest  that 
the  order  which  is  most  effective  in  reducing  the  action  of 
an  organic  ferment  is  also  the  most  effective  when  an  in- 
organic ferment  is  dealt  with. 


CHAPTER  V. 

THE  ACTION  OF    THE    ENZYMES  FOUND  IN   THE   HUMAN 
ALIMENTARY  TRACT. 

i.  Amylase  (ptyalin,  amylopsin,  diastase)  is  the  term 
applied  to  the  enzyme  found  in  the  salivary  and  pancreatic 
secretions,  which  has  the  power  of  acting  upon  starch  and 
producing  from  it  maltose  and  dextrin.  The  ferment  is 
found  in  other  tissues  of  the  body  also,  as  well  as  in  germinat- 
ing cereals  of  all  kinds  (rice,  corn,  oats,  etc.).  The  alimentary 
secretions  of  all  animals  do  not  contain  amylase.  The  saliva 
of  the  dog,  for  instance,  contains  no  starch-splitting  ferment, 
and  the  same  seems  to  be  true  of  all  carnivora.  The  amylase 
of  the  parotid  seems  to  be  present  in  the  human  being  im- 
mediately after  birth,  but  the  starch-splitting  ferment  of  the 
pancreas  does  not  appear  until  a  month  or  more  later. 

We  recognize  the  presence  of  amylase  by  its  power  of  acting 
upon  starch  and  its  ready  destruction  by  heat  rather  than  by 
any  analytical  means  at  our  disposal.  As  with  practically  all 
enzymes,  amylase  has  not  yet  been  obtained  in  a  pure  state. 
Cohnheim  1  has  succeeded  in  obtaining  the  amylase  of  the 
saliva  as  a  gray  powder  of  fairly  constant  composition  by 
acidifying  the  collected  saliva  with  phosphoric  acid  and 
neutralizing  subsequently  with  dilute  calcium  hydroxide. 
The  amylase  is  carried  down  mechanically  with  the  precipi- 
tate of  calcium  phosphate,  and  after  filtering  is  redissolved  by 
the  addition  of  water.  From  this  aqueous  solution  the  amylase 
can  be  ropreci  pita  ted  by  alcohol  in  order  to  further  purify  it. 

'  Cohnheim:  Virchow's  Archiv,  1863,  XXVIII,  p.  241. 

99 


100  PHYSIOLOGY   OF  ALIMENTATION. 

The  amylase  of  the  pancreas  is  obtained  in  a  very  active 
state  by  Robert's  method  of  precipitation  with  alcohol  and 
re-solution  in  water.  The  method  of  Cohnheim  for  obtaining 
the  starch-splitting  ferment  of  the  saliva  has  also  been  applied 
to  the  pancreas,  though  Robert's  method  seems  to  give  a 
more  active  preparation. 

The  most  frequently  utilized  source  of  amylase  to-day  is 
probably  germinating  malt,  which  contains  this  enzyme  in 
enormous  quantities.  Effront's  a  method  of  obtaining  the 
ferment  from  this  source  consists  in  the  extraction  of  finely 
ground  malt  with  water  for  some  time,  filtration,  and  alco- 
holic fermentation  of  the  nitrate  through  the  addition  of 
yeast.  After  a  second  filtration  the  amylase  is  precipitated 
from  the  filtrate  through  the  addition  of  alcohol.  Effront 
obtained  in  this  way  from  every  100  grams  of  malt  3  to  3J 
grams  of  a  white  substance  which,  when  redissolved  in  water, 
was  as  active  as  80  grams  of  the  original  malt. 

Much  discussion  has  arisen  as  to  the  identity  or  non-identity 
of  the  amylase  obtained  from  various  sources.  So  far  as  the 
qualitative  character  of  the  action  of  the  amylase  on  starch  is 
concerned,  there  seems  to  be  no  difference,  whatever  be  the 
origin  of  the  ferment.  Quantitatively  the  pancreatic  amylase 
acts  more  powerfully  than  the  salivary,  but  this  is  explicable 
on  the  basis  of  mere  differences  in  the  concentration  of  the 
enzyme  in  the  two  secretions. 

Other  characteristics,  such  as  differences  in  sensitiveness 
to  heat,  alkalies,  acids,  salts,  etc.,  have  also  been  brought 
forward  in  support  of  the  independent  nature  of  the  starch- 
splitting  ferments  from  different  sources,  but  great  care  must 
be  exercised  in  accepting  these  arguments.  As  already  stated, 
amylase  has  not  yet  been  obtained  in  a  pure  state.  The 
impurities  which  accompany  any  preparation  of  amylase  are 
different,  depending  upon  the  source  of  the  ferment.     Even 

1  Effkont:  Die  Diastasen.  Translated  into  German  by  Bucheler, 
Leipzig  u.  Wien.  1900, 1,  p.  113. 


ACTION  OF   THE  ENZYMES  101 

the  same  source  docs  not  always  yield  the  same  impurities. 
It  is  therefore  entirely  probable  that  the  differences  which 
have  been  assumed  to  exist  in  the  amylase  obtained  from  dif- 
ferent sources  are  only  apparent,  and  depend  upon  the  fad 
that  the  impurities  accompanying  the  ferment  are  different. 
In  this  way  the  same  ferment  is  simply  compelled  to  work 
under  different  external  conditions,  and,  as  will  be  shown 
immediately,  the  medium  in  which  amylase  acts  has  an  im- 
portant influence  upon  its  action.  What  has  been  said  here 
of  amylase  holds  also  for  the  other  ferments. 

Amylase  brings  about  two  changes  when  allowed  to  act 
upon  starch — it  liquefies  the  starch  and  converts  it  into  sugar. 
The  sugar  which  is  formed  by  amylase  when  unmixed  with 
other  enzymes  is  the  disaccharide,  maltose.  When  amylase  is 
allowed  to  act  upon  raw  starch  granules,  the  latter  are  seen 
to  be  gradually  eroded,  and  sugar  is  formed.  Upon  boiled 
starch  amylase  acts  far  more  energetically,  the  conversion 
into  sugar  being  accomplished  in  much  shorter  time.  Accord- 
ing to  Kuhne,  the  amylase  of  the  .saliva  does  not  act  upon  un- 
boiled starches  at  all,  while  that  of  the  pancreas  does.  It  is 
entirely  probable,  however,  that  this  difference  is  only  appar- 
ent and  dependent  upon  the  fact  that  the  concentration  of 
the  amylase  in  the  saliva  is  less  than  that  in  the  pancreatic 
juice.  The  chemical  change  which  starch  suffers  under  the 
influence  of  amylase  is  indicated  in  the  following  formula: 

CioH2o01o  H-HoC^C^H-a^Oii- 

Starch  Water  Maltose 

This  formula  shows  that  starch  undergoes  a  hydration 
when  acted  upon  by  amylase,  but  it  tells  us  nothing  of  the 
mechanism  of  this  change.  That  maltose  is  the  ultimate 
product  of  the  catalytic  change  is  almost  universally  accepted 
but  opinions  differ  widely  as  to  the  intermediate  changes 
which  occur  in  the  starch  before  the  final  stage  of  maltose  is 
reached.  All  observers  are  agreed,  however,  that  dextrin  is 
formed  in  the  process  of  saccharification.     Whether  the  dex- 


102  PHYSIOLOGY  OF  ALIMENTATION. 

trin  is  formed  from  the  starch  and  is  subsequently  changed 
into  sugar,  or  whether  dextrin  and  sugar  are  formed  simul- 
taneously, is  not  yet  settled.  If  the  former  is  ths  correct 
view,  it  would  be  expressed  by  the  formula 

Ci2H2o010  =C12H2oOio.  (1) 

Starch  Dextrin 

Ci2H2o01q4-H20  =  Ci2H22011.  (2) 

Dextrin  Water  Maltose 

If  the  second  theory,  that  of  Museums,  is  the  correct  one, 
the  following  equation  would  hold: 

2  Ci2ff2oO!o+H20=  Ci2H2201i  +Ci2H2oOio. 

Starch  Water  Maltose  Dextrin 

The  majority  of  authors  also  believe  that  the  dextrin  formed 
is  not  all  of  the  same  kind,  that,  in  other  words,  several  dex- 
trins  are  formed,  which  have  been  distinguished  by  different 
names.  The  basis  for  this  belief  lies  in  the  fact  that  the 
dextrins  obtained  at  different  stages  in  the  saccharification 
of  starch  are  not  converted  into  maltose  with  the  same  rapidity 
when  acted  upon  by  amylase  under  normal  circumstances 
or  in  the  presence  of  acids,  salts,  various  organic  substances, 
etc.  It  seems  probable,  however,  that  these  differences  rest 
more  upon  physical  than  upon  chemical  characteristics  of 
the  dextrin.  Dextrin  belongs  to  the  group  of  substances 
known  as  colloids,1  and  the  properties  which  have  been 
considered  characteristic  of  different  dextrins  might  readily 
characterize  one  and  the  same  chemical  substance  in  differ- 
ent physical  states.  A  dextrin  solution  in  which  the  particles 
are  finely  divided  would,  for  example,  be  more  rapidly  con- 
verted into  sugar  than  one  in  which  the  suspended  particles 
are  coarser. 

Amylase  may  be  used  as  a  type  to  illustrate  some  of  the 
characteristics  of  a  ferment.     Amylase  accelerates  a  chemical 

1  See  Chapter  XIV,  Part  2. 


ACTION  OF   THE   ENZYMES.  103 

reaction  which  occurs  also  in  its  absence,  only  then  exceed- 
ingly slowly.  Starch  paste  by  itsolf  kepi  a!  a  suitable  tem- 
perature is  very  slowly  converted  into  maltose.  Amylase 
is  therefore  a  positive  catalyzer.  The  influence  of  tem- 
perature upon  the  activity  of  this  ferment  has  been 
worked  out  by  Kjeldahl.  At  0°  C.  amylase  acts  exceedingly 
slowly,  but  its  activity  increases  rapidly  with  an  increase 
in  temperature  until  35°  C.  is  reached.  From  35°  to  a 
little  above  60°  C.  a  further  but  less  marked  increase  is 
observed.  Beyond  this  point  the  activity  of  the  ferment 
falls  off  rapidly  until  at  70°  C.  it  acts  no  more  energetically 
than  at  about  15°.  A  curve  similar  to  those  shown  on  p.  89 
would  therefore  represent  graphically  the  influence  of  tem- 
perature upon  amylase.1 

The  reaction  which  amylase  catalyzes  is  incomplete  when 
allowed  to  take  place  in  glass,  the  saccharification  coming  to 
a  standstill  when  less  than  half  of  the  total  starch  present  has 
been  converted  into  maltose.  The  exact  point  varies  with  ex- 
ternal conditions  of  temperature,  concentration,  etc.  We  shall 
see  later  that  this  fact  indicates  that  the  action  of  amylase  is 
reversible.  Evidence  of  the  truth  of  this  statement  has  recently 
been  brought  by  Criomer,2  who  has  shown  that  a  ferment 
(perhaps  identical  with  amylase)  which  has  the  power  of 
splitting  glycogen  (an  isomer  of  starch,  and  often  called 
animal  starch)  into  glucose  is  also  able  to  synthesize  glycogen 
from  glucose. 

If  sufficient  time  is  given,  the  amount  of  change  brought 
about  in  a  starch  paste  is  the  same,  no  matter  what  the 
concentration  of  the  amylase. 

The  activity  of  amylase  is  markedly  influenced  by  the 
presence  of  different  chemical  substances  in  the  reaction 
mixture.     Amylase  seems  to  act  best  in  a  neutral  medium. 


1  See  Effront:  Die  Diastasen.     Translated  into  German  by  Buche- 
lbr,  Leipzig,  1900,  I,  p.  119. 

2  Cremer:  Ergebnissed.  Physiol.,  1902,  L,  He  Abth.   p  N0.'>. 


104  PHYSIOLOGY  OF  ALIMENTATION. 

Both  acids  and  alkalies  soon  bring  its  activity  to  a  stand- 
still, even  in  very  moderate  concentrations.  The  influence 
of  acids  upon  amylolytic  activity  is  of  physiological  impor- 
tance, because  the  chewed  food  mixed  with  saliva  passes 
into  the  stomach.  The  concentration  of  the  acid  in  the 
stomach  is  sufficient  to  stop  the  activity  of  the  amylase; 
but,  as  will  be  remembered  from  what  has  been  said  before, 
the  amylase  continues  its  action  for  some  time,  especially 
in  the  cardiac  end  of  the  stomach,  as  the  food  which  passes 
into  this  viscus  is  not  at  once  rendered  acid  by  its  secre- 
tions. 

It  has  been  shown  by  the  work  of  Cannon  that  the  saliva 
does  not  act  best  in  the  concentration  in  which  it  is  poured 
out  upon  the  food,  but  when  diluted  with  about  three  times 
its  bulk  of  water.  The  explanation  of  this  fact  lies  no 
doubt  in  the  dilution  of  the  products  of  amylolytic  activity, 
for  in  a  concentrated  solution  the  point  at  which  the  reac- 
tion comes  to  a  standstill  is  reached  sooner  than  in  a  more 
dilute  one.  In  fact,  most  fermentation  mixtures  which 
have  come  to  a  standstill  will  go  on  further  if  only  water 
is  added.  The  use  of  water  with  meals,  after  thorough 
mastication  of  the  food,  is  therefore  not  only  not  harmful, 
but  useful.  Dilution  of  the  stomach  contents  hastens  the 
activities  of  the  enzymes  here  also.  The  presence  of  water 
in  the  stomach,  moreover,  increases  the  secretion  of  gastric 
juice  and  hastens  absorption.  The  evil  consequences  of  the 
consumption  of  water  with  meals  lie  in  its  use  before  masti- 
cation of  the  food,  thus  preventing  thorough  insalivation  and 
the  good  effects  of  this  process  upon  the  food;  and  in  the  use 
of  too  cold  water,  whereby  the  reaction  velocity  of  all  fer- 
mentative changes  is  markedly  decreased. 

2.  Maltase  (glucase)  is  an  enzyme  the  characteristic  activ- 
ity of  which  lies  in  its  power  of  splitting  maltose  into  two 
molecules  of  dextrose.  It  is  able  to  act  also  upon  starches 
and  dextrins,  but  only  exceedingly  weakly  when  compared 
with  amylase,  the  ultimate  product  from  these  substances 


ACTION  OF   THE  ENZYMES.  105 

also  being  dextrose.  Maltose  is  formed  as  an  intermediate 
product,  so  that  what  was  defined  as  the  characteristic  ac- 
tivity of  maltase  appears  here  also.  It  is  evident  from  this 
that  care  must  be  exercised  in  deciding  whether  a  ferment 
present  in  animal  or  vegetable  tissues  and  capable  of  pro- 
ducing a  sugar  from  starch  is  amylase  or  maltase,  or  whether 
both  are  present.  The  recognition  of  the  first  is  dependent 
upon  the  identification  of  maltose  as  the  end-product  of  the 
reaction,  that  of  the  latter  upon  the  recognition  of  dextrose. 
The  existence  of  maltase  in  the  presence  of  amylase  can  be 
proved  by  isolating  a  ferment  which  splits  pure  maltose  into 
dextrose.  The  recognition  of  amylase  in  the  presence  of 
maltase  is  more  difficult,  and  differences  in  resistance  to 
heat,  chemical  reagents,  etc.,  must  be  utilized  to  bring  about 
their  separation. 

Maltase  seems  to  have  been  first  discovered  by  Bechamp 
in  the  urine,  and  somewhat  later  by  Brown  and  Heron  in  the 
pancreatic  juice  and  in  the  small  intestine.  It  is  found  also  in 
the  saliva.  The  commonest  source  of  maltase  to-day  for  the 
study  of  its  activities  is  corn,  from  which  it  can  be  obtained 
in  a  very  active  state,  by  precipitation  of  a  dilute  acid- 
alcohol  extract  of  this  cereal  with  strong  alcohol.1  The 
ferment  when  obtained  in  this  way  is  not  pure. 

Qualitatively  the  maltase  obtained  from  different  sources 
shows  the  same  action  upon  maltose.  Considerable  differ- 
ences exist,  however,  in  the  resistance  of  this  enzyme  to 
external  conditions  when  obtained  from  different  animal 
tissues  or  cereals.  This  has  been  taken  to  argue  in  favor 
of  the  existence  of  different  maltases.  Since  maltase  has 
not  yet  been  obtained  in  a  pure  state,  however,  we  can- 
not be  sure  whether  the  differences  found  in  the  various 
maltase  preparations  are  due  to  specific  differences  in  the 
ferments  themselves  or  to  differences  in  the  impurities  with 
which  the  preparations  are  contaminated. 

1  Beueiunck:  Centralbl  f.  Bakteriologie,  1898,  xxiii,  2te  Abth. 


106  PHYSIOLOGY  OF  ALIMENTATION. 

Lintner  and  Kroeber  *  give  as  the  optimal  temperature  for 
the  action  of  yeast  maltase  upon  maltose  40°  C.  Below  and 
above  this  point  the  formation  of  dextrose  proceeds  much 
more  slowly.  At  50°  C.  this  maltase  is  almost  entirely 
destroyed.  Cusenier  gives  56°  to  60°  C.  as  the  optimal 
temperature  for  the  maltase  obtained  from  corn.2 

Maltase  is  of  special  biological  interest,  as  it  was  in  a 
study  of  this  ferment  that  the  fundamental  fact  of  the 
reversible  action  of  enzymes  was  first  experimentally  proved  by 
the  interesting  work  of  A.  Croft  Hill.3  For  a  better  under- 
standing of  this  property  of  enzymes  a  few  introductory 
words  are  necessary  to  illustrate  the  general  conceptions  of 
chemical  equilibrium  and  reversion. 

If  a  number  of  substances  capable  of  reacting  chemically 
with  each  other  are  brought  together,  a  reaction  ensues, 
which  after  a  time  comes  to  a  standstill  (practically  speak- 
ing). We.  say  then  that  the  system  is  in  chemical  equilib- 
rium. If,  for  example,  at  a  definite  temperature  chemically 
equivalent  amounts  of  acetic  acid  and  ethyl  alcohol  are 
mixed  together,  a  reaction  ensues  according  to  the  following 
equation: 

CH^COOH +C2H5OH  =CH3COOC2H5  +  H20. 

Acetic  acid  Ethyl  Ethyl  acetate  Water 

alcohol 

The  reaction  takes  place  in  the  direction  from  left  to  right. 
If  chemically  equivalent  amounts  of  ethyl  acetate  and  water 
are  mixed  together,  ethyl  alcohol  and  acetic  acid  are  formed. 
In  other  words,  the  above  reaction  takes  place  from  right 
to  left.  Neither  in  the  first  nor  second  instance  does  the 
reaction  become  complete.     Before  the  given  amounts  of 

1  Lintner  and  Kroeber:  Berichte  d.  deutschen  chem.  Gesellsch., 
1895,  p.  1050. 

2  Quoted  from  Effront:  Die  Diastasen.  Translated  into  German 
by  Bucheler,  Leipzig  u.  Wien,  1900,  I,  p.  225. 

3  Hill:  Jour,  of  the  Chem.  Society,  1898,  LXXLTI,  p.  634;  Berichte 
d.  deutschen  chem.  Gesellsch.,  1901.  XXIV.  p.  1380. 


ACTION  OF   THE   ENZYMES.  107 

acetic  acid  and  ethyl  alcohol,  or  ethyl  acetate  and  water, 
have  undergone  complete  decomposition  the  reaction  comes 

to  a  standstill. 

A  reaction  such  as  wc  have  just  spoken  of,  which  can  lake 
place  from  right  to  left  as  well  as  from  lefl  to  right,  is  called 
a  reversible  reaction.  We  indicate  such  a  reversible  reaction 
as  follows: 

CH3COOH  +C2H5OH  <=>  CH,COOC2H5  +H20. 

Acetic  acid  Ethyl  Ethyl  acetate  Water 

alcohol 

It  can  readily  be  seen  that  when  equilibrium  is  estab- 
lished in  a  reversible  reaction  the  four  substances  reacting 
with  each  other  are  present  in  the  reaction  mixture.  The 
characteristic  feature  of  such  a  condition  of  equilibrium  is 
found  in  the  fact  that  under  the  same  external  conditions 
it  is  always  the  same  no  matter  from  which  side  it  is  reached. 
In  other  words,  it  is  immaterial  whether  chemically  equivalent 
amounts  of  acetic  acid  and  ethyl  alcohol  or  chemically 
equivalent  amounts  of  ethyl  acetate  and  water  are  mixed 
together.  The  condition  of  equilibrium  reached  in  either 
case  is  the  same.1 

Although  we  say  ordinarily  that  when  chemical  equilibrium 
has  been  established  the  reaction  has  come  to  a  standstill, 
this  is  in  reality  incorrect.  When  chemical  equilibrium  is 
established  between  the  two  members  of  a  chemical  equation 
it  really  means  that  the  chemical  changes  are  still  going  on, 
only  the  amount  of  change  in  the  one  direction  is  exactly 
counterbalanced  by  the  reverse  change  in  the  opposite 
direction.     The  reaction  is  therefore  stationary. 

As  has  long  been  known,  maltase  acting  upon  maltose  is 
unable  to  bring  about  its  complete  analysis  into  dextrose. 
The  reaction  comes  to  a  stands! ill  when  some  85  percent  of 
the  original  maltose  is  split.     Hill  now  tried  the  interesting 

1  Pen  Cohen  Physical  Chemistry  lor  Physicians.  Translated  by 
Martin  M.  Fischer,  New  York,  1903,  p.  68. 


108 


PHYSIOLOGY  OF   ALIMENTATION. 


\ 


experiment  of  allowing  yeast  maltase  to  act  at  30°  C.  upon  a 
40-percent  solution  of  dextrose  for  a  number  of  months,  and 
found  that  this  same  ferment,  which  is  able  to  bring  about  the 
analysis  of  the  maltose,  is  also  able  to  bring  about  its  syn- 
thesis from  the  products  of  the  analysis.  Hill  determined 
the  appearance  of  maltose  and  its  gradual  increase  in  the  dex- 
trose solution  by  means  of  the  polariscope  and  copper  reduc- 
tion tests.  Since  maltose  is  able  to  rotate  the  plane  of  polar- 
ized light  more  to  the  right  than  dextrose,  and  since  dextrose 
has  a  greater  reducing  power  than  maltose,  it  is  possible 
through  analysis  to  determine  whether  in  a  mixture  of  the 
two  sugars  one  is  increasing  at  the  expense  of  the  other. 
Column  A  in  the  following  table  shows  how,  under  the  influ- 
ence of  yeast  maltase,  the  rotating  power  of  a  pure  dextrose 
solution  gradually  increases,  while  column  B  shows  how  its 
reducing  power  gradually  decreases.  Columns  C  and  D  indi- 
cate the  percent  of  maltose  contained  in  the  originally  pure 
dextrose  solution,  as  calculated  from  the  figures  obtained  in 
the  first  two  columns.  The  values  obtained  by  the  two 
methods  of  analysis  agree  very  well. 


Duration 
of  experiment 


0  days 
5  " 
14  " 
28  " 
42  " 
70     " 


A. 

Rotation. 


52.5° 
55.0° 
58.3° 
60.3° 
62.7° 
63.6° 


B. 

Reduction. 


100.5 
97.7 
95.8 
94.0 
92.5 
90.6 


C. 

Maltose  in  %. 


0.0 
3.0 

7.4 
10.0 
13.0 
14.0 


D. 

Maltose  in  %. 


0.0 

3.5 

6.8 

10.0 

12.0 

15.0 


Maltase  seems,  therefore,  to  have  a  reversible  action  and 
is  able  not  only  to  split  maltose  into  dextrose,  hut,  also  to  svn- 
fflgp  the  rHgflPfVifirirle  from  the  monosaccharide.  The 
I chemical  reaction  expressing  this  may  be  written  as  follows: 


C12H220ii  +H20  +±  C6Hi203+C6H1206. 

Maltose  Water  Dextrose  Dextrose 


ACTION  OF   THE   ENZYMES.  109 

This  equation  is  entirely  analogous  to  (lie  one  given  on  page 
107.  As  in  the  case  of  ethyl  acetate  and  water,  we  have  here 
also  a  reaction  which  can  take  place  in  either  direction.  No 
matter  from  which  side  we  begin,  the  final  result  is  always  I  he 
same — the  presence  in  the  reaction  mixture  of  maltose  an 
water  side  by  side  with  two  molecules  of  dextrose.  The  onl 
difference  between  the  reaction  discussed  on  page  L07  c\n<\  this 
one  is  that  the  analysis  or  synthesis  of  maltose  occurs  under 
the  influence  of  a  catalyzer.  But,  as  has  been  pointed  out,  a 
catalyzer  only  alters  the  rate  of  a  chemical  reaction  and  does 
not  enter  into  the  reaction  itself  (unless  it  does  so  tempora- 
rily). The  analysis  or  synthesis  of  maltose  would  occur  in  the 
same  way,  and  the  state  of  equilibrium  finally  attained  be  the 
same,  even  if  no  maltase  were  present,  only  under  such  cir- 
cumstances the  velocity  of  the  reaction  would  be  very  low. 
The  system 

Maltose  +  Water  <=±  Dextrose  -f  Dextrose 

is  in  equilibrium  under  the  conditions  existing  in  Hill's  experi- 
ments when  some  85  percent  of  dextrose  exists  beside  about  15 
percent  of  maltose.  It  is  clear  that  such  a  mixture  of  the  two 
sugars  in  water  will  undergo  no  apparent  change  whether  mal- 
tase be  present  or  not.  As  shown  above,  however,  the  reaction 
has  not  ceased,  only  the  chemical  change  in  the  one  direction 
just  counterbalances  that  in  the  opposite,  so  that  outwardly 
everything  remains  the  same.  But  what  must  occur  if  into 
the  above  reaction  mixture  some  maltose  or  some  dextrose  is 
introduced,  or  either  of  these  substances  is  removed?  It  is 
clear  that  this  must  disturb  the  chemical  equilibrium  existing 
between  the  maltose  on  the  one  hand  and  thedextrose  on  the 
other.  Whenever  this  occurs  the  activity  of  maltase  as  an 
agent  hastening  the  establishment  of  a  state  of  equilibrium 
between  these  two  substances  must  come  into  play,  and  must 
either  analyze  or  synthesize  maltose  until  such  a  state  of 
equilibrium  is  again  established.     The  introductioo  of  dex- 


110  PHYSIOLOGY  OF  ALIMENTATION. 

trose  or  the  removal  of  maltose  from  a  reaction  mixture  con- 
taining the  two  sugars  in  chemical  equilibrium  would  there- 
fore be  followed  by  a  synthesis  of  maltose,  while  the  introduc- 
tion of  maltose  or  the  removal  of  dextrose  would  be  followed 
by  an  analysis  of  the  disaccharide  if  other  external  conditions 
remained  the  same. 

3.  Caseinase  (rennin,  rennet)  is  the  name  given  to  a  ferment 
found  in  many  animal  and  vegetable  cells  and  their  secretions, 
which  has  the  power  of  changing  caseinogen  into  casein — 
that  is,  the  power  of  curdling  milk.  In  the  human  being  the 
ferment  is  found  in  the  secretions  of  the  stomach  from  birth. 
Milk-curdling  ferment  is  found  also  in  the  pancreatic  juice, 
and  though  it  differs  somewhat  from  the  caseinase  found  in 
the  stomach  in  its  resistance  to  heat  and  chemical  agents,  it 
is  probably  the  same  substance  and  may  well  be  called  by  the 
same  name. 

A  number  of  authors  have  pointed  out  the  fact  that  case- 
inase always  coexists  with  a  proteolytic  ferment.  In  the  case 
of  the  human  being  (and  certain  other  animals)  caseinase 
accompanies  the  acid-proteinase  (pepsin)  of  the  stomach  and 
the  alkali-proteinase  (trypsin)  of  the  pancreas.  Caseinase, 
moreover,  is  found  in  largest  amount  in  those  portions  of  the 
stomach  where  the  most  acid-proteinase  is  found,  namely,  the 
fundus.  The  constant  association  of  the  two  enzymes  has 
given  rise  to  the  idea  that  they  probably  represent  a  giant 
molecule,  the  different  portions  of  which  have  different  fer- 
mentative functions  and  are  differently  affected  by  external 
conditions.  It  has  been  shown  by  Herzog,  for  example,  that 
antiproteinase  (antipepsin)  added  to  the  combined  ferments 
inhibits  only  the  proteolytic  action,  while  the  milk-curdling 
action  goes  on  undisturbedly.  Digestion  with  weak  acids  will 
at  proper  temperature  quickly  destroy  the  caseinase  con- 
stituent of  the  entire  molecule,  and  by  mechanical  precipita- 
tion Hammarsten  has  succeeded  in  obtaining  a  caseinase  solu- 
tion free  from  any  proteolytic  activity. 

Preparations  of  caseinase  are  obtained  by  extracting,  with 


ACTION  OF   THE  ENZYMES.  Ill 

solvents  of  various  kinds,  the  stomach  of  (lie  calf,  which  con- 
tains the  enzyme  in  enormous  quantities.  Among  these 
sodium  chloride  and  hydrochloric  acid  solutions  may  be  men- 
tioned.  Glycerine  is  also  used  extensively.  When  purer 
preparations  are  required,  precipitation  with  alcohol,  filtra- 
tion, and  re-solution  in  water  are  necessary. 

Caseinase  behaves  like  other  ferments  in  that  it  is  readily 
destroyed  at  a  rather  low  temperature.  A  few  minutes', 
exposure  in  a  neutral  solution  at  70°  C,  or  in  an  acid  solu- 
tion at  63°  C,  suffices  to  do  away  with  all  milk-curdling 
properties.  In  an  alkaline  medium  the  ferment  is  affected 
rapidly  even  at  a  very  low  (room)  temperature.  Though 
active  in  a  faintly  acid  or  alkaline  medium,  caseinase  acts 
best  in  a  neutral  medium  and  at  a  temperature  of  about 
40°.  Below  and  above  this  point  the  rapidity  with  which 
milk  is  made  to  coagulate  falls  off  rapidly. 

The  mechanism  of  the  coagulation  of  milk  has  been  studied 
by  a  number  of  authors.  Briefly  summarized  it  may  be 
stated  as  follows:  Milk  contains  a  protein  substance  to 
which  the  name  caseinogen  has  been  given  (casein  of  Ham- 
marsten),  the  change  of  which  into  casein  (paracasein  of 
Hammarsten)  is  the  essential  change  in  the  curdling  of 
milk.  Casein  is  formed  from  caseinogen  under  a  number 
of  circumstances.  This  occurs  when  acid  is  added  to  the 
milk,  or  when  any  acid-producing  change  occurs  in  the 
milk  such  as  "souring  "  under  the  influence  of  bacteria, 
or  when  an  electric  current  is  passed  through  the  milk. 
But  milk  is  caused  to  coagulate  most  rapidly  in  ordinary 
alimentation  through  the  addition  of  caseinase.  In  the  gastro- 
intestinal tract  two  agencies  are  active  in  bringing  about  the 
coagulation  of  ingested  milk:  first,  the  hydrochloric  acid  of 
the  gastric  juice,  and  secondly,  the  presence  of  caseinase  in 
the  gastric  and  pancreatic  secretions.  Another  source  of 
caseinase  in  the  alimentary  trad  is  found  at  times  in  cer- 
tain bacteria  which  may  be  present. 

When  caseinase  is  added  to  milk  the  latter  soon  sets  into 


112  PHYSIOLOGY  OF  ALIMENTATION. 

a  solid  mass  which  contracts  after  a  time  and  squeezes  out 
a  yellowish  fluid — the  whey.  The  clot  consists  of  casein 
in  the  meshes  of  which  there  is  found  the  fat  of  the  milk. 
The  whey  contains  lactalbumin  and  lactglobulin,  two  pro- 
tein bodies  which  have  nothing  to  do  with  the  curdling  of 
the  milk,  together  with  the  sugar  of  the  milk  and  most 
of  its  salts. 

In  the  coagulation  of  milk  during  ordinary  digestion  three 
substances  are  involved — caseinogen,  caseinase,  and  certain 
salts.  It  was  first  shown  by  Hammarsten  that  calcium 
salts  play  an  important  role  in  the  curdling  of  milk.  As 
will  be  shown  immediately,  however,  calcium  'represents 
only  one  of  a  large  number  of  salts  which  can  influence 
the  coagulation  of  milk.  Various  theories  have  been  pro- 
posed from  time  to  time  to  explain  fehe  interaction  of  the 
three  substances.  These  have  in  the  main  been  of  a  chem- 
ical nature,  and  have  assumed  the  production  of  true  chem- 
ical combinations  between  caseinogen  and  calcium,  etc. 
The  recent  work  of  Conradi  and  of  Loevenhart  speak 
against  this  idea  and  indicate  that  in  the  curdling  of  milk  we 
are  dealing  with  a  physical  process  in  which  the  colloid  casein- 
ogen which  exists  in  ordinary  milk  in  a  liquid  or  sol  state  is 
converted  into  the  solid  or  gel  state  which  we  term  casein. 
Caseinogen  and  casein  (casein  and  paracasein  of  Hammar- 
sten) are  therefore  the  same  chemically,  but. different  physi- 
cally in  that  the  former  consists  of  small  particles  suspended 
in  the  liquid  portion  of  the  milk,  while  the  latter  represents 
these  same  particles  clumped.  The  passage  from  the  sol  to 
the  gel  state  is  influenced  by  the  ferment  caseinase  and  cer- 
tain salts. 

Casein  can  be  precipitated  by  all  methods  used  for  this 
purpose  much  more  easily  than  can  caseinogen.  But  if 
the  proper  concentration  is  employed  the  latter  is  brought 
down  also.  It  is  concluded  from  this  that  casein  exists  in 
a  coarser  state  of  aggregation  than  caseinogen.  Nor  can 
the  differences  which  have  been  said  to  exist  between  case- 


ACTION   OF    THE  ENZYMES.  113 

inogen  and  casein  be  taken  to  indicate  that  they  are  nol  the 
same  chemically,  for  all  the  stated  differences  can  easily  be 

explained  on  the  assumption  that  the  two  represent  physical 
modifications  of  one  and  the  same  substance. 

As  stated  above,  calcium  sails  are  not  the  only  ones 
to  bring  about  a  precipitation  of  casein.  At  the  proper 
concentration  a  large  number  of  salts  cause  the  precipitation 
not  only  of  casein  but  of  caseinogen  as  well.  Arranged  in 
the  order  of  their  effectiveness  the  salts  of  the  different 
metals  read  as  follows: 

(1)  Metals  which  precipitate  neither  casein  nor  caseinogen: 
Sodium,  potassium,  ammonium,  rubidium  (?),  caesium  (?). 

(2)  Metals  which  at  room  temperature  quickly  precipi- 
tate casein,  but  caseinogen  only  after  remaining  at  40°  C. 
for  some  time  or  on  heating  to  a  still  higher  temperature: 
Lithium,  beryllium,  magnesium,  calcium,  strontium,  barium, 
manganese  (ous),  iron  (ous),  cobalt  (ous),  nickel  (ous). 

(3)  Metals  which  precipitate  both  casein  and  caseinogen 
at  room  temperature:  The  remaining  heavy  metals,  includ- 
ing iron  (ic). 

As  we  pass  from  the  first  group  through  the  second  to 
the  third,  the  precipitating  power  of  the  metals  for  both 
casein  and  caseinogen  increases  progressively.1 

1  See  Osborne:  Journal  of  Physiology,  1901,  XXVII,  p.  398;  Con- 
radi:  Mi'inchener medizinalische Wochenschr.  XL VIII,  1901,  (l),p.  17"); 
Loevenhart:  Zeitschrift  fur  physiologist-he  Cheinie,  1904,  XLI,  p.  177. 


CHAPTER  VI. 

THE  ACTION  OF  THE  ENZYMES  FOUND  IN  THE    HUMAN 
ALIMENTARY  TRACT  (Continued). 

4.  Acid-proteinase  (pepsin). — By  this  term  is  understood 
a  proteolytic  ferment  which  acts  only  in  the  presence  of 
an  acid.  Acid-proteinase  is  found  widely  distributed  in 
nature  in  both  animal  and  vegetable  cells.  It  is  found  in 
many  regions  in  the  human  body,  more  especially  in  the 
muscles,  and,  what  interests  us  most  in  this  connection,  in 
the  mucous  lining  and  secretion  of  the  stomach.  Acid- 
proteinase  has  the  power  of  acting  upon  proteins  in  the 
presence  of  certain  acids  and  splitting  these  proteins  into 
a  series  of  simpler  substances.  What  these  simpler  sub- 
stances are  will  be  discussed  further  on. 

Acid-proteinase  is  present  in  the  stomach  of  the  human 
being  from  the  time  of  birth.  Neither  at  this  time  nor  later 
in  life,  however,  do  all  parts  of  the  stomach  contain  it  in 
the  same  amount.  The  cardiac  end  of  the  human  stomach 
contains  much  more  than  the  pyloric  end. 

Pure  preparations  of  acid-proteinase  are  exceedingly  dim- 
cult  to  obtain.  Extraction  of  the  mucosa  of  the  pig's  stomach 
with  a  0.2  percent  hydrochloric  acid  solution  or  with  glycerine 
yields  very  active  preparations.  These  are,  however,  very 
lmpure.  Brucke's  method  of  extraction  of  the  mucous 
membrane  with  dilute  phosphoric  acid  and  subsequent 
neutralization  with  calcium  hydroxide  seems  to  yield  very 
pure  acid-proteinase.  The  enzyme  is  carried  down  mechan- 
ically with  the  precipitate  of  calcium  phosphate,  and  can  be 

114 


ACTIOS  OF   THE   ENZYMES.  115 

subsequently  rcdissolved  in  water.  PEKELHARING  '  claims  to 
have  prepared  the  purest  acid-proteinase  thus  far  obtained 
and  classes  the  enzyme  union-  the  proteins.  His  prepara- 
tion gives  the  well-known  reactions  for  proteins,  and  on 
quantitative  analysis  shows  the  presence  of  carbon,  nitrogen, 
hydrogen,  and  sulphur  in  the  proportions  in  which  they 
exist  in  these  bodies.  As  the  preparation  contains  no  phos- 
phorus it  is  not  considered  a  nucleo-proteid.  In  harmony 
with  the  findings  of  Nencki  and  Sieber,  Pekelharing  looks 
upon  chlorine  as  a  constant  constituent  of  acid-proteinase. 
Should  it  be  shown  ultimately  that  Pekelharing's  enzyme  is 
not  a  pure  substance  it  will  still  have  to  be  looked  upon  as 
the  most  active  preparation  of  this  ferment  obtained  thus  far. 
0.001  milligram  in  6  c.c.  of  a  0.2  percent  hydrochloric  acid 
solution  dissolved  a  flake  of  fibrin  in  a  few  hours. 

The  acid-proteinase  of  Pekelharing  is  able  not  only  to  act 
on  proteins  but  also  curdles  milk.  This  means  that  acid- 
proteinase  and  caseinase  are  probably  parts  of  the  same 
molecule.  As  stated  above,  gastric  juice  contains  a  fat-split- 
ting ferment — lipase — but  the  pepsin  preparation  of  Pekel- 
haring shows  no  fat-splitting  activity.  This  author's  work, 
therefore,  supports  a  view  which  has  been  suggested  by 
Nencki  and  Sieber  before  him,  that  acid-proteinase  and 
caseinase  represent  different  parts  of  a  giant  molecule. 

Brunton,2  and  Friedenthal  and  Miyamota3  have  ex- 
pressed themselves  as  opposed  to  the  conception  of  the  protein 
character  of  pure  acid-proteinase  and  bring  forward  as  proof 
that  they  have  succeeded  in  obtaining  active  acid-proteinase 
preparations  which  do  not  give  any  of  the  reactions  for  pro- 
teins. It  is  also  pointed  out  by  these  authors  that  acid-pro- 
teinase is  not  digested  by  alkali-pro teinase  (trypsin),  which  as 

1  Pekelharing:  Zeitschrift  fur  physiologische  Chemie,  1902  XXXV 
p.  8. 

2  Brunton.  Centralblatt  fur  Physiologie,  1902.  XVI,  p.  201. 

3  Friedenthal  and  Miyamota:  Centralblatt  fur  Physiologie  1901, 
XV,  p.  7s<i;  ibid.,  1902,  XVI,  p.  1, 


116 


PHYSIOLOGY  OF  ALIMENTATION. 


is  well  known  acts  upon  all  proteins  thus  far  studied.  Against 
Friedenthal  and  Miyamota  can  be  brought  the  argument 
that  their  preparations  were  not  very  active  and  so  may 
have  contained  too  little  of  the  pure  enzyme  to  give  the 
protein  reactions.  Further  study  of  the  subject  is,  however, 
necessary  before  the  question  can  be  looked  upon  as  settled. 
Acid-proteinase  acts  only  in  an  acid  medium,  but  the  kind 
of  acid  is  not  immaterial.  Hydrochloric  acid  furnishes  by 
far  the  most  favorable  medium,  but  nitric,  sulphuric,  phos- 
phoric, lactic,  acetic,  tartaric,  etc.,  are  also  active.  Pflei- 
derer,1  who  has  investigated  the  question  physico-chemically, 
comes  to  the  conclusion  that,  broadly  speaking,  different 
acids  favor  the  action  of  acid-proteinase  on  fibrin,  according 
to  their  "avidity,"  those  with  the  greater  "avidity"  acting 
more  powerfully  than  those  with  a  lesser  one.  Since  we  now 
know  that  the  "avidity"  or  "strength"  of  an  acid  is  an 
expression  of  the  number  of  free  hydrogen  ions  it  yields 
upon  solution,  the  above  statement  may  be  said  to  mean 
that  those  acids  which  yield  the  largest  number  of  hydrogen 
ions  when  dissolved  in  water  are  most  powerful  in  furthering 
the  activity  of  acid-proteinase.  The  following  table  may 
serve  to  illustrate  what  has  been  said  as  well  as  serve  as  a 
text  for  that  which  is  to  follow.  The  degree  of  fibrin  diges- 
tion as  measured  by  Grutzner's  method2  is  expressed  in 


Degree  of  color  after 

Name  of  acid, 
all  3^  normal. 

5 
min. 

10 
min. 

20 

min. 

30 
min. 

1 
hr. 

1* 

hrs. 

2 

hrs. 

5 

hrs. 

10 

hrs. 

24 
hrs. 

Nitric 

1 
0 
0 
0 
0 
0 

5 
0-1 
0 
0 
0 
0 

5-6 

1 
0-1 

0 

0 

0 

6 
2 
1 
0 
0 
0 

6 
3-4 
3-4 
0-1 

0 

0 

6 
5 
5-6 
1 
0 
0 

6 
5 
6 
2-3 
0 
0 

6 
5-6 
6 
4 
0 
0 

6 
6 
6 
5-6 
0 
0 

6 
6 

Lactic 

6 

6 

0 

0 

1  Pfleiderer:  Pfluger's  Arch.,  1897,  LXVI,  p.  605. 

2  See  p.  130. 


ACTION  OF   THE   ENZYMES.  117 

figures  from  1  to  6,  according  to  the  amount  of  color  pro- 
duced. In  each  digestion -tube  were  present  the  same  amounts 
of  fibrin  and  pepsin  and  chemically  equivalent  amounts 
of  the  various  acids. 

At  a  somewhat  higher  concentration  (for  example,  1/20 
normal)  both  the  acetic  and  sulphuric,  acid  tubes  would 
have  shown  some  degree  of  fibrin  digestion,  but  the  order 
of  the  table  would  not  have  been  much  different.  With- 
out further  comment,  therefore,  it  is  clear  that  while  the 
effect  of  any  acid  upon  the  proteolytic  activity  of  acid- 
proteinase  is  chiefly  a  function  of  the  number  of  hydrogen 
ions  which  the  acid  yields  on  solution  in  water,  the  indi- 
vidual acids  vary  enough  from  each  other  even  when  the 
number  of  hydrogen  ions  in  the  unit  volume  of  the  digestion 
mixture  is  the  same  to  make  us  inquire  after  the  cause  of 
this  difference.  Sulphuric  acid,  for  example,  which  in 
dilute  solution  is  dissociated  to  about  the  same  degree  as 
hydrochloric,  stands  far  below  this  in  its  power  of  bringing 
about  a  demolition  of  the  protein  molecule.  Now  since 
sulphates  in  general  (sodium  sulphate,  magnesium  sul- 
phate, etc.)  markedly  retard  the  activity  of  acid-protcinase 
even  when  this  is  acting  in  the  presence  of  hydrochloric 
acid,  it  lies  near  at  hand  to  consider  the  S04  constituent 
of  the  sulphuric  acid  and  of  these  salts  as  chiefly  respon- 
sible. Other  salts,  such  as  the  chlorides  and  iodides  of 
sodium,  potassium,  and  ammonium,  also  inhibit  the  diges- 
tion of  a  protein  under  the  influence  of  acid  proteinase  and 
hydrochloric  acid,  but  not  so  markedly  as  the  sulphates. 

The  reason  for  the  individual  differences  between  the 
acids  and  the  effect  of  various  salts  upon  the  velocity  of 
digestion  is  not  yet  entirely  clear.  It  is  evident  that  the 
nature  of  their  action  might  be  various.  In  looking  over 
Pfleiderbr's  tables,  however,  one  is  struck  with  the  parallel- 
ism which  exists  everywhere  between  the  effect  of  the  different 
acids  and  the  various  salts  upon  the  rate  of  digestion  and 
the  degree  of  swelling  which   these  substances   bring  about 


118  PHYSIOLOGY  OF  ALIMENTATION. 

in  fibrin  alone.  As  is  well  known,  fibrin  swells  in  different 
acids,  but  not  to  the  same  degree  in  each.  If  now  the 
acids  are  arranged  according  to  the  degree  in  which  they 
make  fibrin  take  up  water  (swell),  this  order  is  the  same 
as  that  given  above  for  the  effect  of  these  same  acids  on 
digestion  under  the  influence  of  acid-pro teinase.  Sulphuric 
acid,  for  example,  which  stands  very  low  in  the  list  of  acids 
as  favoring  acid-pro  teinase  digestion,  occupies  a  similar 
position  when  the  acids  are  arranged  in  the  order  in  which 
they  cause  fibrin  to  swell.  What  has  been  said  of  the  acids 
holds  also  for  the  salts.  The  more  a  salt  inhibits  the  absorp- 
tion of  water  by  fibrin  (for  example,  a  sulphate)  the  more 
does   this  salt  retard  the   digestion  of  a   protein. 

The  effect  of  various  external  conditions  upon  the  proteo- 
lytic activity  of  acid-proteinase  has  usually  been  attributed 
to  the  effect  of  these  conditions  upon  the  acid-proteinase 
itself.  Unquestionably  external  conditions  can  most  markedly 
influence  the  state  of  the  ferment  itself — it  is  no  doubt  a 
colloid  and  influenced,  as  are  all  colloids,  by  external  con- 
ditions— but  in  the  experiments  which  have  been  cited,  the 
chief  effect  of  the  external  conditions  seems  to  have  been 
on  the  protein  undergoing  digestion.  Bruckb  many  years 
ago  pointed  out  that  the  more  fibrin  has  swelled  the  more 
rapidly  it  is  digested.  The  different  acids  and  salts  in- 
fluence this  swelling  in  different  degrees,  in  consequence  of 
which  the  protein  is  attacked  by  the  acid-proteinase  with 
greater  or  less  ease.  It  seems  to  me  that  this  difference 
between  the  physical  change  which  a  protein  suffers  when 
it  swells  during  the  process  of  peptic  digestion,  and  the 
chemical  change  which  probably  constitutes  the  real  activity 
of  the  proteolytic  ferment  when  the  simpler  digestion- 
products  are  formed,  has  never  been  sufficiently  well  drawn. 
The  two  are  different,  and  differently  influenced  by  external 
conditions. 

The  optimum  concentration  of  hydrochloric  acid  for  the 
activity  of  acid-proteinase  varies  with  the  protein  which 


A  CTION  OF   Til  E   i:.\  ZYM  ES.  119 

is  being  acted  upon.     Hammarsten  gives  0.08  to  0.1   per- 
cenl  for  fibrin;  0.1  percenl  for  myosin,  casein,  and  vegetable 

proteins;  0.25  percent  for  coagulated  white  of  egg. 

Alkalies  and  alkaline  salts  when  present  in  a  digestion 
mixture  are  uniformly  injurious  in  I  heir  action.  If  pro- 
teins are  present  at  the  same  time  with  the  acid-proteinase, 
alkalies  act  less  destructively,  no  doubt  because  the  alka- 
lies combine  with  the  protein.  This  is  indicated  by  the 
Eacl  that  the  same  concentration  of  alkali  acts  the  less 
deleteriously  upon  the  acid-proteinase  the  greater  the  amount 
of  protein  present.1  Of  other  substances  which,  when 
present,  influence  the  activity  of  acid-proteinase  and  which 
are  of  medical  interest,  the  following  may  be  mentioned: 
Alcohol  and  tannic  acid  interfere  with  the  action  of  the 
ferment,  as  do  most  alkaloids  and  carbohydrates.  Bile 
also  belongs  in  this  group,  for  one  part  of  this  substance  is 
able  to  do  away  entirely  with  the  proteolytic  activity  of 
five  hundred  parts  of  gastric  juice.  Caffein  and  theobromin 
further  the  action  of  the  enzyme.2 

Within  certain  limits  the  rapidity  with  which  acid-pro- 
teinase splits  a  protein  increases  with  an  increase  in  the 
quantity  of  the  ferment  present  in  the  reaction  mixture. 
But  in  no  case  is  the  digestion  of  the  protein  complete  unless 
the  products  of  the  reaction  are  removed.  An  accumulation 
of  the  products  of  digestion  retards  markedly  the  further 
analysis  of  the  protein.  It  will  be  shown  further  on  that 
this  is  probably  dependent  upon  the  fact  that  the  action  of 
acid-proteinase  is  reversible,  and  that  the  ferment  synl  he- 
sizes   from   the  products  of  the  digestion   the  protein  itself, 

'  See  Langley.  Journal  of  Physiology,  18S2,  111,  pp.  L'53  mid  283; 
Langley  and  Edkins:  ibid.,  1886,  VII,  p.  371. 

Wroblewski.  Zeitschrift  fur  physiologischc  Cliemie,  1S95,  XXI, 
p.  1;  also  Buchner.  Berichte  der  deutschen  chem.  Gesellschaft,  1897, 
XXX1I1,  p.  1110;  Laborde:  Comptes  rendus  Soc.  biol.,  1S09,  LI,  p. 
821;  Xirenstein  and  Schipf.  Archiv  KirVerdauungskrankheiten,  1902, 
VIII,p.559.  Bruno.  Pawlow's  Workoi  the  Digestive  Glands.  Trans- 
lated by  Thompson    London,  1902,  p.  15S. 


120  PHYSIOLOGY  OF  ALIMENTATION. 

in  a  way  analogous  to  that  described  for  the  action  of  mal- 
tase  on  maltose. 

Acid-proteinase  is,  like  other  ferments,  very  sensitive  to 
temperature.  At  0°  C.  it  is  scarcely  active.  From  this  point 
to  35°  C.  the  velocity  of  its  action  increases  progressively, 
attaining  an  optimum  between  35°  and  50°  C.  Beyond  this 
point  its  activity  diminishes.1  In  a  neutral  solution  the  fer- 
ment is  in  a,  few  minutes  destroyed  at  55°  C.  The  presence 
of  hydrochloric  acid  protects  the  ferment  against  destruction 
by  heat,  so  that  when  present  in  the  concentration  in  which 
the  acid  is  found  in  the  stomach,  the  ferment  is  destroyed  only 
slowly  until  65°  C.  is  reached.  Peptones  and  certain  salts  also 
have  a  protecting  influence.2  As  with  other  ferments,  the 
concentration  of  the  acid-proteinase  itself  in  a  pure  solution 
influences  the  temperature  at  which  it  is  most  rapidly 
destroyed. 

When  natural  or  artificial  gastric  juice  (a  solution  of  acid- 
proteinase  in  dilute  hydrochloric  acid)  is  allowed  to  act  upon 
a  protein,  such  as  fibrin,  the  following  changes  are  observed. 
The  fibrin  begins  to  swell  and  its  superficial  portions  become 
translucent,  until,  under  favorable  conditions  of  temperature, 
the  insoluble  protein  is  rendered  soluble.  If  given  time 
enough,  the  acid  alone  will  bring  about  a  solution  of  the  fibrin; 
but  if  acid-proteinase  is  present  this  change  occurs  much  more 
rapidly.  If  the  enzyme  is  employed  in  a  neutral  solution  the 
protein  is  not  dissolved.  Acid  and  ferment  together  are 
therefore  necessary  to  bring  about  the  rapid  change  from  the 
protein  to  the  soluble  product.  The  soluble  product  consists, 
as  will  be  seen  presently,  of  a  mixture  of  a  number  of  chemical 
substances,  which  are  distinguished  from  the  original  protein 
upon  which  the  acid-proteinase  acted  by  their  ready  solubility 
in  water  and  their  ready  diffusibility  through  animal  and 
vegetable  membranes.     These  properties,  it  will  be  noticed, 

iv.  Wittich:  Pfluger's  Arch.,  1869,  II,  p.  193;  ibid.,  1870,  III, 
p.  339. 

2  Biernacki.  Zeitschr.  fur  Biol.,  1892,  XXVIII,  p.  453. 


ACTIOS  OF  THE  ENZYMES.  121 

stand  in  marked  contrasl  to  those  of  the  original  protein  sub- 
stance— for  instance,  fibrin — which  is  insoluble  and  readily 
held  back  by  a  filter  or  animal  membrane.  It  is  those  prop- 
erties of  the  products  of  gastric  digestion  which  give  them  the 
] tower  of  being  easily  taken  up  by  the  mucous  membrane  of 
the  alimentary  tract. 

Our  conceptions  of  the  nature  of  the  products  formed  when 
proteins  are  digested  in  the  presence  of  acid-proteinase  have, 
within  the  last  few  years,  been  markedly  altered,  more  espe- 
cially through  the  investigations  of  Zunz,1  Pfaundler,2  Law- 
row,3  Malfatti,4  Salaskin,5  Langstein,6  Emil  Fischer  7 
and  Abderhalden.7  The  work  of  all  these  authors  indicates 
that  acid-proteinase  working  in  the  presence  of  an  acid  causes 
a  cleavage  of  the  protein  molecule  into  substances  of  a  much 
simpler  chemical  composition  than  we  formerly  supposed. 
Where  we  once  believed  that  proteoses  and  "peptones,"  in 
the  sense  in  which  Kuhne  used  this  term,  constituted  the 
final  products  of  gastric  digestion,  we  now  know  that  a  large 
number  of  substances,  which  were  formerly  looked  upon  as 
produced  only  in  pancreatic  digestion,  are  also  formed.  In 
experiments  in  which  acid  and  acid-proteinase  have  been 
allowed  to  act  long  enough,  there  have  been  found,  besides  the 
more  complex  proteoses  and  "peptones,"  the  following  simple 
compounds:    leucin,    tyrosin,    alanin,    phenylalanin,   amino- 

1  Zunz:  Zeitschrift  fur  physiologische  Chemie,  1899,  XXVIII,  p.  132. 

2  Pfaundler.  Zeitschrift  fur  physio logische  Chemie,  1900,  XXX, 
p.  90. 

3  Lawrow:  Zeitschrift  fur  physiologische  Chemie,  1899,  XXVI,  p. 
513;  ibid.,  1901,  XXXIIl,p.  312. 

1  Malfatti:  Zeitschrift  fur  physiologische  Chemie,  1900,  XXXI,  p. 
43. 

6  Salaskin:  Zeitschrift  fur  physiologische  Chemie,  1901,  XXXII,  p. 
592. 

"Langstein:  Hofmeister's  Beitrage  zur  chemischen  Physiologic, 
1901,  I.  !«.  .107. 

'  Kmil  Fisoheh  and  A  i-.ki  i,ii  \  i.mkn  .  Zeitschrift  fur  physiologische 
Chemie,  1903,  XXXIX,  p.  81. 


122  PHYSIOLOGY  OF  ALIMENTATION. 

valerianic  acid,  aspartic  acid,  glutamic  acid,  and  lysin.  It 
will  be  seen  later  that  these  compounds  are  the  same  as 
those  formed  in  the  action  of  alkali-proteinase  (trypsin)  on 
protein,  and  we  must  in  consequence  ascribe  to  the  gastric 
juice  much  greater  digestive  importance  so  far  as  the  proteins 
are  concerned  than  heretofore. 

An  essential  difference  exists,  however,  in  the  velocity 
with  which  the  two  enzymes  bring  about  the  decomposition 
of  protein  into  these  simpler  substances,  alkali-proteinase 
acting  much  more  rapidly  than  acid-proteinase.  The  degree 
of  the  splitting  is  also  different  in  the  two,  trypsin  causing 
the  total  cleavage  of  much  more  of  the  original  protein 
than  pepsin.  Trypsin  must,  therefore,  generally  speaking, 
be  considered  the  more  powerful  of  the  two  ferments. 

5.  Alkali-proteinase  (trypsin)  is  the  term  applied  to  the 
proteolytic  enzyme  found  in  the  pancreatic  juice  and  in  a 
large  number  of  tissues,  not  only  of  the  human  being,  but 
other  animals  as  well.  The  ferment  was  discovered  by 
Claude  Bernard  in  the  middle  of  the  last  century,  and  has 
since  then  served  as  an  object  of  study  to  scores  of  investiga- 
tors. The  ferment  is  present  in  the  pancreatic  juice  of  the 
human  foetus  from  before  birth.  Absolutely  pure  alkali-pro- 
teinase has  never  been  prepared,  and  even  relatively  pure 
preparations  are  not  easy  to  obtain.  Simple  extraction  of 
the  fresh,  finely  minced  gland  with  a  saturated  sodium  chlo- 
ride solution  gives  a  very  active  preparation.  Extraction  of 
the  gland  with  chloroform  water  for  several  days  has  been 
recommended  by  Salkowski.  Very  active  and  stabile  alco- 
holic and  glycerine  extracts  of  the  proteolytic  enzyme  can 
also  be  prepared.  Mays  l  has  studied  the  problem  very 
carefully,  and  has  perhaps  gotten  the  purest  trypsin  thus  far 
obtained.  For  the  details  of  his  method  the  original  must 
be  consulted.  While  pancreatic  juice  obtained  from  a  pan- 
creatic   fistula   contains    other   ferments   besides    alkali-pro- 

1  Mays:  Zeitschr.  fur  physiologische  Chemie.  1903,  XXXVIII,  p.  428. 


ACTION  OF   Till:  ENZYMES.  123 

teinase,  it  contains  none  of  the  ordinary  intracellular  ferments 
present  in  simple  extracts  of  the  gland  itself.  Pancreatic 
juice  obtained  by  Pawlovv's  or  some  similar  method  repre- 
sents, therefore,  an  excellent  solution  with  which  to  study 
the  activities  of  the  alkali-proteinase. 

Alkali-proteinase  will  act  in  an  alkaline,  neutral,  or  even 
faintly  acid  medium.  The  medium  acting  most  favorably  has 
an  alkaline  reaction.  Kanitz,1  who  has  recently  investigated 
this  problem,  states  that  the  action  of  the  enzyme  is  largely 
independent  of  the  nature  of  the  alkali  or  alkaline  salt  used  to 
obtain  the  alkaline  reaction,  and  is  determined  solely  by  the 
number  of  hydroxy  1  ions  present  in  the  solution.  A  1/200 
to  1/70  normal  solution  of  the  alkali  in  regard  to  the  hydroxyl 
ions  is  the  optimum  one.  An  alkalinity  greater  than  this 
acts  deleteriously  upon  the  enzyme.  The  ferment  acts  very 
well  in  a  neutral  medium,  but  is  rapidly  destroyed  in  the 
presence  of  an  acid,  even  of  the  concentration  of  the  hydro- 
chloric acid  of  the  gastric  juice. 

The  nature  of  the  protein  upon  which  alkali-proteinase 
acts  is  not  without  influence  upon  the  rapidity  of  the  splitting 
process.  '  Unboiled  fibrin  cannot  well  be  used  in  making 
comparative  tests  with  trypsin,  as  it  is  too  rapidty  digested. 
Boiled  fibrin  is  digested  more  slowly,  and  this  substance, 
or  boiled  white  of  egg,  is  ordinarily  used  in  work  on  tins 
ferment.  Even  the  last-named  is  rapidly  digested  by  alkali- 
proteinase.  The  protein  acted  upon  does  not  first  swell, 
as  is  the  case  with  acid-proteinase,  but  breaks  up  at  once 
into  small  particles  which  rapidly  go  into  solution. 

Alkali-proteinase  is  very  sensitive  to  temperature.  It  acts 
best  at  about  40°  C,  being  rapidly  destroyed  above  this 
point.  Below  40°  C.  the  activity  of  the  enzyme  falls  off 
gradually,  but  it  is  still  recognizable  even  :ii  0°  C.  70°  C. 
is  ordinarily  given  as  the  highest  temperature  at  which 
alkali-proteinase  will  exhibit  any  proteolytic  activity. 

1  Kanitz.  Zeitschr.  i'.  physiol.  Chem.,  L902,  XXXVII,  i>.  7.".. 


124  PHYSIOLOGY   OF  ALIMENTATION. 

Alkali-proteinase  shows,  in  common  with  other  ferments, 
an  increase  in  the  velocity  of  reaction  with  an  increase  in  the 
concentration  of  the  enzyme.  This  holds  true,  however, 
only  within  certain  limits  of  time,  concentration  of  both 
enzyme  and  protein,  etc.  In  infinite  time  a  small  amount 
of  the  ferment  will  bring  about  as  much  protein  digestion 
as  a  larger  one.  In  no  case  is  all  the  protein  split  into  the 
digestion  products  to  be  discussed  below.  Unless  the 
products  of  digestion  are  removed  as  soon  as  formed  the 
proteolysis  is  incomplete,  or,  as  it  is  ordinarily  put,  an 
accumulation  of  the  products  of  digestion  interferes  with  the 
further  action  of  the  enzyme.  This  is  probably  due  to  the 
fact  that  the  activity  of  the  enzyme  is  reversible.  When  the 
products  of  the  protein  digestion  are  removed  by  dialysis  as 
soon  as  formed,  a  small  amount  of  the  enzyme  will  split  an 
indefinite  amount  of  the  protein. 

When  alkali-proteinase  is  allowed  to  act  upon  proteins, 
the  protein  molecule  is  broken  up  into  a  number  of  simpler 
substances.  According  to  the  generally  accepted  view,  the 
decomposition  of  the  protein  is  brought  about  by  a  series  of 
successive  cleavages.  Shortly  after  the  ferment  has  begun 
its  work,  there  can  be  recognized  the  proteoses,  and  later 
the  peptones,  in  the  sense  in  which  Kuhne  used  these  terms. 
Before  the  ultimate  products  of  tryptic  digestion  are  reached, 
substances  which  in  their  chemical  complexity  stand  between 
them  and  the  peptones,  the  peptides  of  Emil  Fischer  and 
Abderhalden,1  are  formed.  These  peptides  represent  com- 
binations of  amino-acids,  and  depending  upon  whether  two, 
three,  four,  or  many  molecules  of  the  same  or  different 
amino-acids  enter  into  the  composition  of  the  peptide,  we 
distinguish  between  di-,  tri-,  tetra-,  and  polypeptide  bodies. 
The  ultimate  products  of  tryptic   digestion  are  mono-  and 


1  Emil  Fischer  and  Abderhalden:  Zeitschrift  fur  physiologische 
Chemie,  1903,  XXXIX,  p.  81;  Abderhalden:  Lehrbuch  d.  physiol. 
Chemie,  Berlin,  1906,  Eiweissstoffe. 


ACTION  OF  THE  ENZYMES.  125 

diamino-acids,  many  in  number  and  differing  markedly  from 
the  protein  itself  or  any  of  the  intermediate  products.  In 
*,he  passage  from  the  proteins  to  the  ultimate  digestion 
products  we  find  that  the  substances  become  progressively 
more  simple.  Physically  we  pass  from  those  which  are 
typical  colloids,  that  is  to  say,  amorphous  substances  with 
high  molecular  weights,  practically  no  diffusibility,  and  no 
osmotic  pressure,  to  crystalline  bodies  of  a  low  molecular 
weight  and  of  a  ready  diffusibility.  Whereas  the  original 
substances  are  insoluble  or  only  slightly  soluble,  the  ultimate 
products  are,  generally  speaking,  freely  soluble.  Qualita- 
tively, the  digestion  under  the  influence  of  alkali-proteinase 
does  not  differ  materially  from  that  under  acid-proteinase; 
quantitatively,  alkali-proteinase  is  the  more  powerful  enzyme, 
producing  the  substances  to  be  enumerated  below  much  more 
rapidly  and  in  greater  quantities  than  when  acid-proteinase 
is  used. 

In  order  to  obtain  the  end  products  of  alkali-proteinase 
digestion  for  study,  it  is  best  to  allow  pure  pancreatic  juice 
obtained  from  a  Pawlow  pancreatic  fistula  to  act  upon  a 
protein,  such  as  fibrin.  The  mixture  is  covered  with  toluol 
or  some  other  antiseptic  which  prevents  the  development 
of  bacteria  but  does  not  interfere  with  the  activity  of  the 
alkali-proteinase,  and  the  whole  is  kept  at  a  suitable  tem- 
perature for  varying  periods  of  time.  Many  of  the  products 
of  alkali-proteinase  digestion  can  be  found  shortly  after  the 
ferment  has  been  allowed  to  act  upon  the  protein,  but  cer- 
tain of  the  rare  products  cannot  be  found  insufficient  quan- 
tities until  the  reaction  mixture  has  been  allowed  to  stand 
even  for  months.  In  order  to  get  a  conception  of  the  quan- 
titative relations  between  the  various  digestion  products  .it 
any  desired  time,  the  action  of  the  ferment  can  be  stopped 
by  boiling  the  reaction  mixture.  Frequently  the  autodiges- 
tion  of  the  pancreas  and  other  organs  has  been  used  for  the 
study  of  the  products  of  alkali-proteinase  digestion,  hut  in 
these  cases  it  cannot   be  said  with  certainty  that  some  of 


126  PHYSIOLOGY  OF  ALIMENTATION. 

he  products  formed  are  due  to  the  action  of  alkali-proteinase 
alone  and  not  to  the  action  of  intracellular  enzymes  exist- 
ing beside  the  alkali-proteinase. 

The  following  is  a  list  of  the  amino-acids  that  have  been 
isolated  from  various  proteins.  In  spite  of  the  great  physi- 
cal differences  between  the  proteins  obtained  from  different 
sources,  they  are  very  similar  in  chemical  constitution.  When 
any  protein  is  split  hydrolytically,  be  this  under  the  influence 
of  alkali-proteinase  or  acid-proteinase,  or  as  it  is  often  accom- 
plished in  the  laboratory,  through  the  action  of  strong  acids 
or  alkalies,  the  same  series  of  simple  substances  is  always  ob- 
tained which  consists  almost  entirely  of  amino-acids.  All 
proteins,  moreover,  yield  the  same  amino-acids,  only  the  pro- 
portion which  these  bear  to  each  other  in  the  different  pro- 
teins is  different,  and  sometimes  one  or  the  other  of  the 
acids  may  be  entirely  absent.  In  order  to  render  what  is  to 
follow  more  intelligible,  the  next  paragraph  contains  a  list 
of  the  amino-acids  which  have  been  obtained  not  only  through 
the  action  of  alkali-proteinase,  but  also  by  other  methods  of 
hydrolysis.  Most  of  these  acids  have,  however,  been  isolated 
from  at  least  certain  proteins  through  the  action  of  alkali- 
proteinase  alone.  It  will  be  noticed  that  certain  of  those 
enumerated  have  already  been  mentioned  as  products  of 
peptic  digestion. 

Glycocoll,  alanin,  aminoisovalerianic  acid,  leucin,  isoleucin, 
serin,  aspartic  acid,  glutamic  acid,  lysin,  arginin,  histidin, 
cystin,  phenylalanin,  tyrosin,  prolin,  oxyprolin,  tryptophan.1 

The  diamino-acids  in  the  above  series,  such  as  lysin,  arginin, 
and  histidin,  are  often  spoken  of  as  the  hexone  bases,  and  con- 
stitute with  ammonia  the  basic  products  of  the  hydrolysis  of 
proteins. 

The  following  diagram,  as  arranged  by  Abderhalden,  may 
serve  to  indicate  the  scheme  according  to  which  the  proteins 
are  under  the  influence  of  a  ferment   (or  other  hydrolytic 

1  Abderhalden.  Lehrbuch  d.  physio).  Chemie.    Berhn,  1906,  p.  160. 


ACTIOX  OF    THE  ENZYMES 


127 


-  -z  rt 


Qr 

r- 

GO                C             •  -  - 

i\-d    1 

o 

<       'Z        a 

1 

o 
.5 

— c        c 


_        —         c 


128  PHYSIOLOGY  OF  ALIMENTATION. 

agent)  broken  into  successively  simpler  compounds  until  the 
amino-acids  are  finally  reached.  From  the  albumins,  for 
example,  are  derived  first  of  all  the  album oses,  which  may  well 
be  looked  upon  as  being  made  up  of  long  chains  of  amino- 
acids.  These  now  break  up  into  shorter  chains  constituting 
the  peptones.  In  the  analysis  of  albumin  we  are  able  to 
recognize  this  stage  in  digestion  by  the  appearance  of  certain 
color  reactions  (biuret  test),  which  it  will  be  seen  later  l  are 
given  by  certain  polypeptides  which  have  been  produced  syn- 
thetically. The  peptones  may  therefore  be  looked  upon  as  a 
mixture  of  polypeptides.  These  polypeptides  now  break  up 
into  still  simpler  chains  of  amino-acids  passing  more  or  less 
directly  through  the  stages  of  hexa-,  penta-,  tetra-,  etc.,  pep- 
tides until  the  simple  mono-  and  diamino-acids  are  reached. 
The  peptides  giving  a  biuret  test  pass  over  without  a  break 
into  those  which  do  not  give  this  reaction.  It  is  clear,  there- 
fore, that  little  by  little  the  name  "peptone"  must  disappear 
to  give  way  to  well-defined  chemical  compounds.  Transitional 
forms  of  all  degrees  of  chemical  complexity  exist  between  the 
peptones  on  the  one  hand  and  the  simple  amino-acids  on  the 
other.  The  diagram  does  not  show,  of  course,  the  way  in 
which  any  protein  is  hydrolyzed,  but  rather  one  or  two 
schemes  according  to  which  this  may  occur.2 

1  See  p.  142. 

2  Abderhalden:  Lehrbuch  d.  physiol.  Chemie,  Berlin,  1906,  p.  206. 


CHAPTER  VII. 

THE  ACTION  OF  THE  ENZYMES  FOUND    IN  THE    HUMAN 
ALIMENTARY    TRACT    (Continued). 

6.  The  Recognition  and  Quantitative  Estimation  of  the 
Proteinases. — The  methods  which  have  been  devised  for  the 
qualitative  recognition  of  the  proteolytic  ferments  consist  for 
the  most  part  in  an  exposure  of  a  readily  obtainable  protein, 
such  as  fibrin  from  blood  or  white  of  egg  to  an  extract  of  the 
animal  or  vegetable  organ  which  is  being  tested,  and  "finding 
that  this  is  dissolved.     Care  must  be  taken  in  each  case,  of 
course,  to  provide,  through  the  addition  of  an  acid  or  an  alkali 
to  the  mixture,  an  acid,  neutral  or  alkaline  reaction  depending 
upon  whether  acid-,   ampho-,  or  alkali-proteinase   (pepsin, 
papain,  or  trypsin)  is  being  tested  for.     Instead  of  utilizing 
the  disappearance  of  the  protein  as  evidence  of  the  presence 
of  a  proteolytic  ferment,  the  appearance  in  the  reaction  mix- 
ture of  certain  well-established  products  of  proteolytic  activity 
may  also  be  used.     Since  acids,  for  example,  can  by  them- 
selves bring  about  the  destruction  of  a  protein  (but  only  after 
a  long  time  at  ordinary  temperatures), the  time  element  also 
plays  a  role  in  these  qualitative  tests,  in  that  the  destruction 
of  the  protein  and  the  appearance  of  digestion  products  must 
occur  within  a  relatively  short  time.      The  actual  time  con- 
sumed in  bringing  about  the  total  solution  of  a  given  amount 
of  protein  may  therefore  be  used  as  an  index  to  the  amount 
of  ferment  present,  a  larger  amount  of  ferment,  under  other- 
wise similar  conditions,  bringing  about  a  total  digestion  more 
rapidly  than  a  smaller  one. 

129 


130  PHYSIOLOGY  OF  ALIMENTATION. 

The  methods  which  have  been  devised  for  the  quantitative 
estimation  of  proteolytic  ferments  are  various  and  still 
exceedingly  unsatisfactory.  For  the  most  part,  no  absolute 
but  only  comparative  estimations  of  the  ferment  content  of 
any  organ  or  secretion  can  be  made.  As  with  the  other  fer- 
ments, it  is  not  possible  to  obtain  the  proteolytic  ferments  in 
anything  even  approximating  a  pure  state  without  tremendous 
and  incalculable  loss,  so  that  direct  estimations  are  out  of  the 
question.  We  have  to  content  ourselves  therefore  with  com- 
parative studies,  in  which  we  can  say  a  definite  mixture 
digests  a  chosen  quantity  of  a  protein  more  or  less  rapidly 
than  an  arbitrarily  established  standard.  From  the  degree 
of  difference  we  can  get  some  idea  of  the  relative  amounts  of 
proteolytic  ferment  present  in  the  different  reaction  tubes,  but 
this  only  within  certain  well-defined  limits  of  time  and  limits 
of  concentration  of  ferment  and  protein.  Of  the  various 
methods  and  their  modifications  which  have  been  devised 
from  time  to  time  for  the  quantitative  estimation  of  pro- 
teolytic ferments,  only  those  are  mentioned  of  which  an  under- 
standing is  necessary  for  what  is  to  follow  in  this  volume. 

(a)  Griltzner's  1  Method. — This  is  a  colorimetric  method  in 
which  fibrin  from  ox-blood  is  used.  The  fibrin  obtained  by 
whipping  fresh  blood  is  finely  chopped  and  washed  in  water, 
after  which  it  is  stained  in  a  carmine  solution.  After  another 
thorough  washing  in  water  this  carmine-stained  fibrin  is  pre- 
served in  glycerine.  When  a  test  is  to  be  made  the  colored 
fibrin  is  thoroughly  washed  in  water  and  a  weighed  amount 
introduced  into  each  of  the  digestion  mixtures  to  be' tested. 
As  the  fibrin  is  digested  the  reaction  mixture  is  colored  red, 
from  the  depth  of  which,  when  compared  with  an  arbitrarily 
established  scale,  deductions  can  be  made  regarding  the  rela- 
tive digestive  power  of  the  different  mixtures. 

(b)  Mett's  Method  consists  in  a  determination  of  the  amount 
of  coagulated  egg  albumin  digested  out  of  capillary  tubes. 

1  Grutzner:  Pfluger's  Archiv,  1874,  VIII,  p.  452. 


ACTION  OF   THE  ENZYMES.  131 

Glass  tubes  1  to  2  mm.  in  diameter  arc  drawn  full  of  fresh 
white  of  egg  and  dipped  for  exactly  a  minute  into  water 
having  a  temperature  of  95°  C,  in  which  the  albumin  coagu- 
lates. After  the  tube  has  been  allowed  to  cool  slowly  it  is 
cut  into  short  pieces  and  these  are  dropped  into  the  digestion 
mixtures  to  be  studied.  The  number  of  millimeters  of  em- 
ulate digested  out  of  the  tube  is  determined  by  the  help 
of  a  low-power  microscope  and  scale  from  which  the  digestive 
power  of  one  mixture  as  compared  with  that  of  another  may 
be  determined.  According  to  a  principle  first  declared  by 
Schutz  the  amount  of  proteolytic  ferment  present  in  the 
various  reaction  mixtures  is  proportional  not  to  the  number 
of  millimeters  of  albumin  digested  out  of  the  tubes  but  to 
their  square.  A  digestion  mixture  which  dissolves  2  mm.  of 
albumin  out  of  a  tube  is  supposed  to  contain  not  twice  as  much 
proteolytic  ferment  as  one  which  digests  only  1  mm.  out  of 
a  tube,  but  four  times  as  much. 

Mett's  method,  though  exceedingly  simple,  is  by  no  means 
free  from  error. 

(c)  Spriggs'  Method. — Spriggs  1  has  devised  a  method  for 
determining  quantitatively  the  rate  at  which  a  coagulable 
protein  is  digested  under  the  influence  of  different  proteolytic 
ferments  which  for  simplicity  and  accuracy  is  far  superior 
to  the  ordinary  methods  employed  for  this  purpose.  Spriggs' 
method  takes  advantage  of  a  physical  change — a  decrease  in 
viscosity  which  occurs  in  a  protein  solution  when  this  is  acted 
upon  by  a  proteolytic  ferment.  In  order  to  measure  this 
change  in  viscosity  use  is  made  of  the  viscosimeter  of  Ostwald, 
illustrated  in  Fig.  19a,  which  allows  an  experimenter  to  deter- 
mine accurately  the  time  required  for  a  measure*  1  amount 
of  liquid  contained  in  A  to  flow  through  the  capillary  tube 
B  into  C.  The  greater  the  viscosity,  the  greater,  of  course, 
will  be  the  time  required  for  a  liquid  to  flow  Through  the 
capillary  tube. 

'Spriggs:  Zeitschr.  f.  physiol.  Chem.,  L902,  XXXV,  p.   165. 


132 


PHYSIOLOGY  OF   ALIMENTATION. 


With  the  use  of  such  an  instrument  Spriggs  found  that 
during  digestion  the  viscosity  of  a  solution  of  a  coagulable 
protein  gradually  decreases.  This  decrease  in  viscosity 
corresponds  with  a  chemical  change  in  the  protein  undergoing 
digestion  from  the  state  in  which  it  is  coagulable  by  heat 


V 

^^B 

2 
Hour 

(b) 


Fig.  19. 


into  that  in  which  it  is  not  coagulable  by  this  means, — in 
other  words  (to  speak  not  very  accurately),  from  the  albu- 
mins into  the  peptones. 

If  the  change  in  the  viscosity  of  the  protein  undergoing 
digestion  is  expressed  in  the  form  of  a  curve,  one  similar  to 
that  shown  in  Fig.  19  (6)  is  obtained.  As  can  readily  be  seen, 
the  viscosity  of  the  protein  solution  decreases  at  first  very 
rapidly,  later  more  slowly,  until  finally  it  runs  almost  parallel 
with  the  base-line.  When  this  line  of  unchanging  viscosity 
is  reached,  the  larger  part  of  the  coagulable  protein  has 
been  converted  into  the  uncoagulable. 


ACTION  OF  THE   ENZYMES.  133 

The  curve  representing  the  decrease  in  the  viscosity  of  a 

protein  solution  can  be  expressed  mathematically  when  it 
becomes  possible  to  calculate  the  relations  which  exist  be- 
tween the  velocity  of  digestion  and  the  amount  of  pro- 
teolytic ferment  present. 

7.  Antiproteinase  (antipepsin  and  antitrypsin). — Under  the 
heading  antiproteinase  we  understand  a  substance  discovered 
by  Weinland,1  which  has  the  power  of  markedly  inhibiting 
by  its  presence  the  action  of  the  proteolytic  enzymes.  Anti- 
proteinase is  therefore  one  of  the  so-called  antiferments. 
Antiproteinase  can  be  obtained  from  a  number  of  sources — 
the  mucous  membrane  of  the  stomach  and  intestines,  but, 
best  of  all,  from  various  intestinal  worms,  especially  ascaris. 
A  description  of  the  method  by  which  antiproteinase  can  be 
obtained  from  ascaris  will  suffice  to  indicate  the  method  by 
which,  in  general,  this  substance  can  be  obtained  from  any  of 
the  tissues  or  fluids  in  which  it  is  present  (see  below). 

A  very  active  though  impure  preparation  of  antiproteinase 
can  be  obtained  by  simply  grinding  up  a  number  of  the  intes- 
tinal worms  with  quartz  sand.  The  addition  of  this  ground-up 
mass  to  an  acid-proteinase  or  alkali-proteinase  solution 
markedly  inhibits  the  activity  of  these  ferments.  A  better 
preparation  of  the  antiproteinase  can  be  obtained  by  sub- 
jecting the  ascaris  paste  to  great  pressure  and  collecting 
and  filtering  the  fluid  which  is  squeezed  out.  The  anti- 
ferment  contained  in  this  very  active  juice  can  be  further 
purified  by  adding  alcohol  to  it,  whereby  the  antiproteinase  is 
precipitated  as  soon  as  the  concentration  of  the  alcohol  in  the 
mixture  exceeds  85  percent.  The  substances  (impurities) 
which  are  precipitated  before  the  concentration  of  the  alcohol 
reaches  60  percent  may  be  filtered  off  without  danger  of 
losing  the  antiproteinase.  The  precipitate  of  antiproteinase 
brought  down  by  the  So  percent  alcohol  settles  to  the  bottom 


'Weinland:  Zeitschr.  f.  Biologie,   L902,  XLIV,  p.    1;  ibid.,  1902, 
XLIV,  p.  45. 


134  PHYSIOLOGY   OF  ALIMENTATION, 

and  may  at  the  end  of  twenty-four  hours  be  filtered  off. 
After  washing  in  96  percent,  then  100  percent  alcohol,  and 
finally  with  ether,  the  precipitate  is  dried  over  sulphuric  acid. 

The  antiproteinase  obtained  in  this  way  is  a  somewhat 
sticky  powder  which  is  readily  soluble  in  water,  and  which  is 
still  contaminated  with  some  impurities.  The  isolation  of  the 
antiferment  is  accompanied  by  a  falling  off  in  its  activity. 
The  activity  of  the  alcohol-precipitated  antiproteinase  when 
redissolved  in  water  is  less  than  half  that  of  the  original  juice 
obtained  from  extraction  of  the  ground-up  worms. 

The  following  experiments  carried  out  with  fibrin  obtained 
from  pig's  blood,  which  is  exceedingly  sensitive  toward  pro- 
teolytic ferments,  may  serve  to  show  how  markedly  anti- 
proteinase inhibits  the  action  of  alkali-  and  acid-proteinase. 

Exp.  A.  Two  tubes  each  containing  8  c.c.  water,  0.04  gm.  sodium 
carbonate,  0.015  gm.  alkali  proteinase,  and  several  pieces  of  fibrin,  but 
the  one  in  addition  7  c.c.  of  ascaris  extract,  the  other  an  equal  amount 
of  water,  are  both  put  into  the  incubator  at  37°  C.  At  the  end  of  two 
hours  the  fibrin  in  the  tube  containing  no  ascaris  extract  (antiprotein- 
ase) has  entirely  disappeared.  The  fibrin  in  the  tube  containing  the 
antiproteinase  is  still  entirely  unchanged  after  six  days,  and  even  on 
the  eleventh  day  of  the  experiment  one-third  of  the  fibrin  is  still  un- 
digested. 

Exp.  B.  Two  tubes  each  containing  7  c.c.  water,  0.23  gm.  hydro- 
chloric acid,  0.015  gm.  acid-proteinase,  and  several  pieces  of  fibrin,  but 
the  one  8  c.c.  of  ascaris  extract,  the  other  an  equal  amount  of  water, 
are  put  into  the  incubator  at  37°  C.  The  fibrin  in  the  tube  contain- 
ing no  antiproteinase  is  dissolved  at  the  end  of  one  hour.  The  fibrin 
in  the  tube  containing  the  ascaris  extract  is  unchanged  on  the  fourth 
day,  and  on  the  ninth  day  only  a  trace  of  the  fibrin  seems  to  have  been 
dissolved. 

Antiproteinase  is  comparatively  sensitive  toward  heat. 
Boiling  for  one  and  a  half  minutes  suffices  to  entirety  do  away 
with  the  protective  properties  of  an  ascaris  extract.  Heating 
for  ten  minutes  to  60°  C.  does  not  injure  the  antiproteinase, 
but  heating  for  the  same  length  of  time  to  80°  C.  reduces  its 


ACTION  OF   THE  ENZYMES.  135 

activity  markedly.  If  the  ascaris  extract  is  kepi  at  {.)5°  C. 
for  ten  minutes,  it  has  lost  its  protective  power  altogether. 

At  ordinary  room  temperature  ascaris  extract  keeps  very 
well  when  1  to  2  percent  of  sodium  fluoride  have  been  added 
to  it  to  prevent  the  development  of  bacteria.  Under  these 
conditions  Weinland  has  kept  an  extract  for  eight  months 
without  apparent  loss  in  the  power  of  the  juice  to  inhibit  the 
action  of  proteolytic  enzymes. 

We  have  in  the  foregoing  paragraphs  spoken  of  antipro- 
teinase  as  though  it  were  a  single  substance.  It  is  possible 
that  there  exist  several  antiproteinases,  though  this  question 
is  still  unsettled.  It  may  be  that  there  exists  an  antialkali- 
proteinase  (antitrypsin)  and  an  antiacid-proteinase  (anti- 
pepsin),  but  further  experiments  must  be  made  to  settle  this 
point  definitely. 

8.  Why  the  Alimentary  Tract  Does  Not  Digest  Itself. — 
Weinland 's  discovery  of  antiproteinase  (antipepsin  and  anti- 
trypsin) is  of  fundamental  physiological  importance,  giving 
us,  as  it  does,  a  partial  explanation  of  the  immunity  which 
"living  "  tissues  possess  towards  the  proteolytic  enzymes.  It 
is  a  well-known  fact,  for  example,  that  the  intestinal  worms — 
nematodes,  trematodes,  cestodes,  etc. — are  not  acted  upon 
by  the  secretions  of  the  stomach,  pancreas,  and  small  intes- 
tine, which  so  readily  and  rapidly  bring  about  the  digestion 
of  the  ordinary  proteins  that  enter  the  alimentary  tract  as 
food.  In  the  same  way  we  know  that  cysticerci,  the  larvae 
of  tapeworms,  must  pass  through  the  stomach  in  order  to 
get  into  the  intestine,  where  they  develop  into  the  adult 
animals.  In  this  passage  through  the  stomach  they  are  sub- 
jected to  the  action  of  the  gastric  juice;  this  digests  the  sac 
in  which  the  larva  is  contained,  as  well  as  the  body  of  the 
larva,  the  head  and  neck  only  being  able  to  pass  on  undigested 
into  the  intestine.  From  these  fragments  the  adult  develops, 
and  this  in  spite  of  the  fact  that  the  growing  animal  is  daily 
bathed  in  streams  of  intestinal  contents  which  are  charged 
with  most  active  proteolytic  enzymes.     We   know   that  a 


136  PHYSIOLOGY  OF  ALIMENTATION. 

tapeworm  may  exist  for  months,  even  years,  in  the  intestine 
of  a  man  or  other  animal. 

Similarly  mysterious  has  appeared  to  us  the  immunity 
which  both  the  stomach  and  small  intestine  possess  against 
their  own  secretions.  The  stomach  is  not  digested  by  the 
gastric  juice,  nor  the  duodenum  when  the  pylorus  opens. 
Neither  is  any  portion  of  the  small  or  large  intestine,  under 
normal  circumstances,  acted  upon  by  the  pancreatic  juice 
which  passes  through  it. 

The  hypotheses  which  have  been  proposed  from  time  to  time 
to  explain  this  immunity  of  intestinal  parasites  and  alimen- 
tary tract  have  been  many  and,  for  the  most  part,  of  a  vital- 
istic  nature.  Claude  Bernard  believed  that  the  epithelial 
covering  of  the  intestinal  tract  protected  the  underlying  tissues 
from  digestion,  but  this  idea,  besides  explaining  nothing ; 
stands  in  contradiction  to  the  facts  of  pathology,  which  show 
that  the  absence  of  epithelial  covering  (for  instance,  in  ulcers 
of  the  gastro-intestinal  tract  from  any  cause  whatsoever)  is 
by  no  means  always,  in  fact  only  at  times,  accompanied  by  a 
loss  of  the  underlying  muscular  or  other  tissues.  These  sub- 
epithelial structures  are  therefore  just  as  immune  against 
digestion  as  the  epithelium  itself. 

Nor  can  Pavy's  theory,  which  assumes  that  the  stomach  is 
not  digested  because  it  is  protected  through  the  alkalinity 
of  the  blood,  be  looked  upon  as  any  more  serviceable.  The 
blood  is,  first  of  all,  not  alkaline,  but  neutral  in  reaction,  and, 
secondly,  Pavy's  explanation  is  of  no  value  when  we  deal 
with  the  intestine,  the  contents  of  which  at  no  time  possess 
the  decided  acid  properties  of  those  of  the  stomach  and  are 
at  times  perhaps  even  alkaline.  The  remaining  theories 
which  have  been  proposed  from  time  to  time  need  not  be  dis- 
cussed, for  they  have  almost  without  exception  covered  up 
the  problem  at  hand  by  attributing  to  the  intact  mucosa 
"living"  properties  which  we  could  never  hope  to  find  in 
"dead"  matter.  As  is  well  known,  the  "dead"  mucosa 
of   the    stomach   undergoes   partial    digestion^    as    seen   in 


ACTION  OF  Till:    ENZYMES.  137 

the  post-mortem  excoriations  of  the  gastric  mucous  mem- 
brane. 

Weinland's  experiments  give  us  a  ready  explanation  of  the 
long-well-established  facts  which  have  been  outlined.  The 
mucous  membrane  of  the  stomach  and   intestine  contains 

antiproteinase;  so  also  do  the  adult  intestinal  worms.  In 
the  case  of  the  cysticerci  only  the  head  and  neck  of  the 
larvae  contain  antiproteinase,  in  consequence  of  which  the 
remaining  portions  of  the  young  parasites  are  digested.  In 
the  same  way  we  may  assume  that  the  greater  ease  with 
which  cooked  meats  are  digested  than  raw,  is  due,  in  part  at 
least,  to  the  fact  that  in  them  the  antiproteinase  is  destroyed 
by  the  heat  used  in  preparing  the  meat. 

Many  facts  indicate  that  antiproteinase  is  widely  dis- 
tributed throughout  the  body,  being  present  in  probably 
all  tissues  with  the  exception  of  the  purely  fatty  ones.  It 
is  entirely  probable  that  antiproteinase  exists  also  in  the 
insectivorous  plants,  which  through  their  proteolytic  secre- 
tions are  able  to  digest  the  animals  they  have  caught  without 
being  acted  upon  by  these  secretions  themselves.  That 
"living"  organs,  such  as  the  spleen,  when  introduced  into  the 
stomach  are  able  to  withstand  the  action  of  the  gastric  juice 
is  dependent  upon  the  presence  of  antiproteinase  in  these 
organs.  In  the  same  way,  extracts  of  liver  and  muscle  are 
able  to  decrease  markedly  the  digestive  activity  of  acid- 
proteinase,  which  indicates  that  antiproteinase  is  present 
in  them.  The  same  is  true  of  blood-serum  and  red  blood- 
corpuscles.  The  discovery  that  antiproteinase  exists  in  the 
liquid  portion  of  the  blood  seems  to  indicate  that  this  ferment 
must  exist  in  every  part  of  the  body. 

Without  discussing  the  subject  more  fully,  which  would 
take  us  too  far  afield,  it  may  not  be  amiss  to  point  out  what 
an  important  physiological  nMc  this  universal  distribution 
of  the  antiproteinase  must  play,  and  what  pathological  con- 
sequences may  accompany  its  hick  or  overproduction  when 
it  is  remembered  that  proteolytic  ferments  (acid-  and  alkali- 


133  PHYSIOLOGY  OF  ALIMENTATION. 

proteinase)  are  found  in  practically  every  tissue  of  the  body 
A  change  in  the  proper  balance  between  ferments  and  anti- 
ferments  can  easily  be  imagined  to  be  accompanied  by  pro- 
found changes  in  the  activities  of  any  organ. 

The  probable  role  which  a  lack  of  antiferment  can  play 
in  the  production  of  gastric  and  intestinal  ulcers  deserves 
special  mention.  It  is  readily  apparent  from  what  has  gone 
before  that  if  the  stomach,  for  example,  does  not  digest 
itself  because  the  mucosa  contains  antiacid-proteinase,  a 
lack  of  this  protective  principle  would  allow  the  gastric 
secretion  to  take  effect  upon  the  mucosa  as  well  as  upon  any 
food  which  passes  through  the  stomach.  What  holds  for  the 
stomach  is  true  of  the  intestinal  tract  in  general.  In  the 
absence  of  experiments  regarding  this  point,  it  is  useless  to 
discuss  the  causes  which  might  lead  to  such  a  lack  of  anti- 
ferment  in  different  portions  of  the  alimentary  tract.  A 
large  number  of  toxic  causes  can  be  imagined  as  capable  of 
so  interfering  with  the  normal  activity  of  the  alimentary 
mucous  membrane  as  to  lead  to  an  inadequate  production 
of  antiproteinase,  or  none  at  all.  That  bacterial  toxins 
and  various  mineral  poisons  are  capable  of  producing  ulcera- 
tions of  the  gastro-intestinal  tract  is  a  well-known  fact. 
Whether  all  or  some  of  them  act  as  indicated  could  readily 
be  determined  by  experiment. 

Special  mention  must  be  made  of  the  round  ulcers  of  the 
stomach.  In  these  cases  the  general  pathological  blood 
condition  so  often  found  in  these  cases  might  be  the  pre- 
disposing condition  which  favors  the  inadequate  production 
of  antiproteinase  in  certain  regions  of  the  stomach.  Some 
authors  have  expressed  the  view  that  an  occlusion  of  the  blood- 
supply  of  circumscribed  areas  of  mucous  membrane  in  the 
stomach  lies  at  the  basis  of  round  ulcers  in  this  viscus.  It 
is  certainly  true  that  an  experimental  occlusion  of  the  artery 
supplying  the  mucous  membrane  of  the  stomach  or  intestine 
is  almost  constantly  followed  by  an  ulcer.  The  lack  of 
blood-supply  would  in  this  case  have  to  be  looked  upon  as  the 


ACTION  OF   THE  ENZYMES.  139 

cause  which  led  to  the  injury  of  the  cells  of  the  mucous 
membrane,  which,  with  their  consequent  inadequate  supply 
of  antiproteinase,  were  digested  by  the  proteolytic  ferments 
present  in  the  alimentary  tract. 

In  cases  of  round  ulcer  of  the  stomach  yet  another  factor 
besides  lack  of  antiproteinase  plays  a  rule  in  the  production 
of  the  lesion,  namely,  a  hyperacidity  of  the  gastric  juice. 
While  this  hyperacidity  has  by  several  authors  been  looked 
upon  as  being  involved  in  the  etiology  of  round  ulcer,  just 
how  it  was  involved  could  not  be  said.     The  experiments  of 
Weinland  give  us  a  clue.     While  antiproteinase  is  able  to 
protect    fibrin   against    digestion    by   a    pepsin-hydrochloric 
acid  mixture,  it  is  able  to  do  so  only  within  certain  limits 
of  concentration  of  the  hydrochloric  acid.     When  the  con- 
centration of  the  hydrochloric  acid  exceeds  a  certain  point 
the  antiproteinase  is  only  partially  able  to  inhibit  the  action 
of  the  acid-proteinase,  so  that  the  fibrin  slowly  goes  into 
solution.     We    can    imagine    the    hyperacidity    of    patients 
affected  with  round  ulcer  to  play  a  similar  role,  in  that  the 
excessive    acid   present    prevents    the   antiproteinase   from 
adequately  protecting  the  stomach-wall.      But  the  hyper- 
acidity can  by  no  means  be  considered  even  the  chief  etio- 
logical factor,  for  if  it  were,  gastric  ulcers  should  be  diffuse 
affairs,  while  they  are  instead  more  or  less   localized   and 
often  intimately  connected  with  local  vascular  disturbances. 
The  resistance  which  the  submucous  tissues  of  the  alimen- 
tary tract  (such  as  the  musculature)  usually  offer  to  the 
digestive  fluids  that  bathe  them  must  also  be  attributed  to 
the  presence  of  antiproteinase  in  them.     In  harmony  with 
this  idea  we  must  also  assume  that  when  the  ulceration  of 
the  alimentary  tract  extends  beyond  the  mucosa  the  involved 
tissues  have  first  been  rendered  susceptible  by  causes  which 
lead  to  the  presence  of  an  inadequate  supply  of  the  anti- 
ferment. 

The  parallelism  which  exists  between  the  proteinases  and 
antiproteinases  on  the  one  hand,  and  the  toxins  and  antitoxins 


140  PHYSIOLOGY  OF  ALIMENTATION. 

on  the  other,  will  occur  to  every  one.  The  mucous  mem- 
brane of  the*  alimentary  tract  is,  by  virtue  of  its  contained 
antiproteinase,  "immune"  against  the  "toxic"  proteinases 
which  daily  pass  over  it. 

A  second  reason  why  the  tissues  of  the  alimentary  tract 
as  well  as  the  tissues  of  the  body  in  general,  are  not  acted 
upon  by  the  ferments  present  in  them  may  reside  in  the 
chemical  constitution  of  the  substances  making  up  the  cells 
themselves.  As  Abderhalden1  has  pointed  out,  the  different 
proteins  contained  in  an  organ  are  by  no  means  acted  upon 
by  the  proteinases  with  the  same  ease.  The  substances  mak- 
ing up  the  connective  tissues,  such  as  elastin  and  spongin  for 
example,  are  acted  upon  scarcely  at  all  by  a  pepsin-hydro- 
chloric acid  mixture  or  trypsin.  This  property  is  connected 
with  the  chemical  constitution  of  the  substances  concerned, 
which  contain  those  amino-acids  in  largest  amounts  whose 
presence  offers  the  greatest  resistance  to  hydrolysis  of  the 
protein  molecule.  It  might  well  be  possible,  therefore,  that 
living  cells  are  endowed  with  properties  which  enable  them  to 
so  modify  the  proteins  absorbed  by  them  as  to  render  them  in- 
capable of  being  acted  upon  by  the  ferments  contained  in  the 
cells.  Only  a  very  slight  change  in  the  chemical  constitution 
of  a  compound  will  make  it  impossible  for  a  ferment  to  attack 
it,  for,  as  is  well  known,  the  ferments  are  dependent  in  a 
most  limited  way  upon  the  stereochemical  construction  of 
the  molecules  upon  which  they  are  capable  of  acting. 

9.  On  the  Reversible  Action  of  the  Proteinases. — The 
question  of  the  means  by  which  the  simple  digestion-prod- 
ucts of  the  proteins  are  again  built  up  into  the  complicated 
albumins,  globulins,  etc.,  which  we  find  in  the  organism  has 
within  the  last  few  years  been  much  debated.  Of  first  in- 
terest in  this  connection  are  the  researches  of  Emil  Fischer,2- 

'  Abderhalden:    Lehrbuch  d.  physiol.  Chemie,  Berlin,  1906,  p.  510. 

2  Emil  Fischer:  Berichte  d.  d.  chem.  Gesellsch.,  1906,  XXIX,  p.  530, 
where  references  to  the  individual  papers  of  the  author  will  be 
found. 


ACTION  OF  THE  ENZYMES.  141 

and  with  him  of  Emil  Abderhalden1  and  their  pupils,  on  the 

chemical  synthesis  of  proteins.  Even  though  no  more  than 
perhaps  a  few  of  the  methods  employed  by  these  workers 
to  bring  about  these  syntheses  arc  of  a  character  which  we 
c:ut  imagine  as  possible  within  living  cells,  this  work  must 
for  all  time  furnish  the  foundation  upon  which  further  ad- 
vances in  the  chemistry  and  physiology  of  the  proteins  must 
build. 

Proceeding  on  the  hypothesis  that  the  protein  molecule  rep- 
resents a  long  series  of  amino-acids  chemically  joined  to  each 
other  in  various  combinations,  Emil  Eischer  showed  that  it  is 
possible  to  link  two  or  more  amino-acids  together  and  obtain 
a  series  of  chemically  more  complex  compounds  known  as 
'peptides.  If,  for  example,  one  molecule  of  glycocoll  is  com- 
bined with  a  second  molecule  of  the  same  substance  the 
dipeptide  glycyl-glycin  is  obtained.  In  a  similar  way  leucyl- 
leucin  can  be  obtained  through  the  union  of  two  molecules 
of  leucin,  and  alanyl-alanin  from  the  union  of  two  of  alanin. 
All  these  are  dipeptides.  It  is  possible,  however,  to  make 
three,  four,  five,  six,  etc.,  amino-acid  molecules  enter  into 
chemical  combination  with  each  other  and  so  obtain  tri-, 
tetra-,  penta-,  hexa-,  or  polypeptides.  A  large  number  of 
such  peptides  have  been  prepared,  as  examples  of  which  the 
following  may  be  cited:  2 

Dipeptides:  Glycyl-alanin,  alanyl-glycin,  alanyl-leucin, 
leucyl-glycin,  glycyl-tyrosin,  leucyl-prolin,  etc. 

Tripeptides :  Leucyl-glycyl-glycin,    leucyl-alanyl-alanin. 

Tetrapeptides:  Tetraglycin,  dileucyl-glycyl-glycin,  dialanyl- 
cystin. 

Pentapeptides :  Pentaglycin,  leucyl-tetraglycin. 

The  means  by  which  such  syntheses  are  accomplished  are 
various,  and  the  number  of  combinations  possible  very  great. 
Let  us  ask  now  whether  they  are  of  more  than  chemical  in- 

1  See  Abdekhalden's  excellent  Lehrbuch  d.  physiol.  Chenrie,  Berlin, 
190<),  Eiweissstoffe. 

2  Abdeuhalden:  1.  c.,  p.  19G. 


142  PHYSIOLOGY  OF  ALIMENTATION. 

terest,  and  whether  they  actually  represent  combinations  of 
amino-acids  such  as  are  produced  in  the  action  of  ferments 
or  acids  on  proteins  of  various  kinds. 

That  such  is  the  case  can  be  shown  first  of  all  by  certain 
chemical  tests.  In  the  analysis  of  proteins  we  encounter  a 
group  of  substances  ordinarily  called  peptones,  which  are 
characterized  by  their  power  of  giving  certain  reactions  such 
as  the  biuret  test.  It  is  of  great  interest,  therefore,  that 
many  of  the  peptides  which  have  been  produced  synthetically 
also  give  the  biuret  test.  While  the  dipeptide  glycyl-glycin 
and  the  tripeptide  triglycin  give  no  biuret  reaction,  this  is 
positive  with  the  tetrapeptide  tetraglycin.  Dialanylcystin 
gives  a  biuret  reaction,  while  the  higher  peptides  containing 
seven  and  more  amino-acids  in  the  molecule,  such  as  leucyl- 
pentaglycin,  give  a  red  biuret  test  which  seems  identical 
with  that  given  by  the  peptones  derived  from  silk.  Phos- 
photungstic  acid,  which  is  abundantly  used  as  a  precipitant 
for  the  simple  digestion-products  of  proteins,  will  also  precipi- 
tate many  of  the  synthetic  peptides.  Certain  of  the  amino- 
acids  which  are  only  difficultly  soluble  in  water  yield  peptides 
which  are  readily  soluble.  The  reverse  is  often  observed  in 
the  analysis  of  proteins.  When,  moreover,  amino-acids  hav- 
ing a  sweet  taste  are  joined  together  chemically  they  yield 
substances  having  a  bitter  taste.  It  is  a  well-known  fact 
that  the  ordinary  peptones  have  a  bitter  taste. 

Certain  of  the  peptides  which  have  been  artificially  produced 
can  be  split  into  amino-acids  by  pancreatic  juice  in  the  same 
way  as  the  peptides  formed  in  an  ordinary  digestion  mixture.1 

With  these  remarks  on  the  synthesis  from  amino-acids  of 
substances  which  seem  to  agree  in  their  chemical  and  biologi- 
cal character  with  the  peptones  we  will  try  to  see  if  there  is 
any  experimental  evidence  at  hand  to  indicate  that  from 
substances  standing  close  to  the  class  of  peptones  others 
giving  the  reactions  of  the  albumins  may  be  obtained.     It 

1  Abderhalden:  1.  c,  p.  201. 


ACTIOS  OF  THE  ESZYMES.  143 

looks  as  though  this  further  synthesis  of  albuminous  sub- 
stances has  been  accomplished  and  by  means  which  we  can 
well  imagine  active  in  the  living  organism. 

Of  first  interest  in  this  direction  is  the  work  of  Okouneff, 
who,  in  1S95,  showed  that  through  the  action  of  trypsin  on  a 
concentrated  solution  of  proteoses  the  latter  suffers  a  physi- 
cal change  in  that  flakes  appear  in  it,  or  in  that  the  whole 
assumes  a  jelly-like  consistency.  This  change  in  consist- 
ency (increase  in  viscosity)  has  been  shown  to  occur  not  only 
under  the  influence  of  alkali-proteinase  (trypsin),  but  also 
acid -proteinase  (pepsin)  and  ampho-proteinase  (papain). 
It  is  a  change,  therefore,  which  is  brought  about  in  a  solu- 
tion of  proteoses  by  any  of  the  ordinary  so-called  proteo- 
lytic ferments. 

What  is  the  character  of  this  change  in  viscosity?  This 
question  has  been  investigated  by  a  number  of  observers 
from  both  a  chemical  and  a  physical  standpoint,  and  the 
results  obtained  by  each  indicate  very  strongly  that  the  proc- 
ess of  the  formation  of  "plastein,"  as  the  above  is  called, 
represents  a  reversion,  under  the  influence  of  the  proteolytic 
ferments,  of  proteoses  into  more  complicated  proteins.  From 
a  chemical  standpoint,  proof  in  this  direction  has  been  brought 
especially  by  Sawjalow,1  who  has  succeeded  in  obtaining 
from  a  proteose  solution  upon  which  a  proteolytic  ferment 
had  been  acting  for  some  time,  and  which  originally  had  been 
free  from  this  reaction,  a  coagulum  on  boiling  after  the  addi- 
tion of  acetic  acid.  This  is  a  reaction  which,  it  is  well  known, 
is  considered  characteristic  of  the  albumins. 

The  change  which  occurs  when  "plastein"  is  formed  has 
been  investigated  from  a  physical  standpoint  by  Herzog,2 
and  to  him  belongs  the  credit  of  recognizing  in  it  the  reversible 
activity  of  a  proteolytic  ferment. 

'Sawjalow:  Pfliiger's Archiv,  1901, LXXXV,  p.  171;  Centralblatf 
fur  Physiologie,  L903,  XVI,  p.  625. 

■  IIeuzog.  Zeitschrift  fur  physiologische  Chemie,  1903,  XXXIX,  p. 
305. 


144  PHYSIOLOGY  OF  ALIMENTATION. 

As  proof  that  the  formation  of  "plastein  "  indicates  that  a 
proteolytic  ferment  has  synthesized  from  the  proteose  solu- 
tion a  substance  or  substances  which  lie  nearer  the  original 
protein  than  the  proteoses,  the  following  may  be  said: 

We  became  familiar  on  p.  131  with  Spriggs'  observation 
that  a  protein  solution  undergoing  digestion  under  the  in- 
fluence of  acid-proteinase  (pepsin)  and  hydrochloric  acid 
suffers  a  decrease  in  viscosity,  and  that  this  decrease  occurs 
rapidly  at  first  and  then  more  slowly.  When  a  solution  of 
proteoses  and  peptones  (ordinary  commercial  "peptone  ") 
has  added  to  it  an  artificial  gastric  juice  the  mixture  is  found 
to  increase  in  viscosity,  at  first  only  slowly  and  then  very 
rapidly.  We  have,  in  other  words,  exactly  the  reverse  of  what 
occurred  before.  This  seems  to  justify  the  conclusion  that 
acid-proteinase  (pepsin)  is  able  not  only  to  catalyze  the 
analysis  of  a  protein  but  also  to  catalyze  its  synthesis  from 
the  products  of  digestion.  What  has  been  said  holds  not 
only  for  acid-proteinase  (pepsin)  but  also  for  alkali-  and 
ampho-proteinase  (trypsin  and  papain). 

If  the  above  is  true  and  the  formation  of  "plastein  "  is 
really  to  be  looked  upon  as  representing  a  synthesis  of 
protein  which  occurs  under  the  influence  of  a  proteolytic 
ferment,  then  we  should  expect  that  the  same  external  con- 
ditions which  favor  or  hinder  the  activity  of  a  proteolytic 
ferment  in  hastening  the  analysis  of  a  protein  should  favor 
or  hinder  in  the  same  way  the  activity  of  this  ferment  when 
it  is  hastening  the  synthesis  of  a  protein.  Thanks  to  the 
researches  of  Weiniand,1  we  are  familiar  with  a  substance, 
antiproteinase  (antitrypsin,  antipepsin) ,  which  retards  (prac- 
tically prevents)  most  markedly  the  activities  of  the  pro- 
teolytic ferments.  The  addition  of  a  small  amount  of 
anti-proteinase,  obtained,  for  example,  from  the  body  of  the 
intestinal  worm  ascaris,  to  a  digestion  mixture  of  protein  and 
proteolytic  ferment  practically  prevents  the  latter  from  act- 

1  See  p.  133. 


ACTION  OF  THE  ENZYMES.  145 

ing  upon  the  protein.  In  the  same  way  ascaris  extract  pre- 
vents the  synthesis  of  protein  (formation  of  "plasiein")  when 
it  is  added  in  a  corresponding  amount  to  a  reaction  mixture 
consisting  of  proteoses  and  a  proteolytic  ferment. 

The  constant  association  of  a  milk-curdling  ferment  with  a 
proteolytic  ferment — the  association  of  caseinase  with  acid-, 
alkali-,  and  ampho-proteinase  wherever  these  ferments  have 
been  isolated — has  given  rise  to  the  idea  to  which  attention 
has  already  been  called  elsewhere,  that  these  two  ferments  are 
united  in  a  giant  molecule,  but  that  different  portions  of  this 
molecule  have  different  activities.  It  is  of  interest,  therefore, 
to  add  in  this  connection  that  antiproteinase,  which  reduces 
so  markedly  the  proteolytic  activity  of  the  giant  molecule, 
does  not  affect  its  milk-curdling  power. 


CHAPTER  VIII. 

THE  ACTION  OF  THE  ENZYMES    FOUND  IN  THE   HUMAN 
ALIMENTARY  TRACT  (Concluded). 

io.  Protease  (erepsin). — The  observation  of  Salvioli,  Hof- 
meister,  Neumeister,  and  others  that  peptone  solutions  when 
brought  in  contact  with  pieces  of  still  living  intestinal  mucous 
membrane  no  longer  give  a  biuret  reaction  after  the  lapse  of 
some  time,  that  is,  disappear,  has  usually  been  interpreted 
as  evidence  indicating  that  the  small  intestine  has  the  power 
of  synthesizing  protein  from  the  products  of  protein  digestion. 
It  has,  in  other  words,  been  generally  believed  that  the 
peptones  which  are  formed  in  the  course  of  ordinary 
digestion  are  built  up  again  into  more  complex  bodies — those 
giving  no  biuret  reaction — in  their  passage  through  the 
intestinal  wall.  Within  recent  years  Cohnheim  1  has  re- 
peated some  of  these  older  experiments,  but  in  attempting 
to  find  corroborative  evidence  for  the  ordinary  explanation 
by  the  discovery  of  a  larger  amount  of  coagulable  protein 
in  the  intestinal  wall  or  its  surrounding  liquids  after  the  biuret 
reaction  had  disappeared  from  the  peptone  solution  than 
before,  his  endeavors  proved  unsuccessful.  He  found  instead 
that  in  place  of  an  increase  in  the  amount  of  coagulable 
protein  he  really  got  an  increase  in  the  amount  of  crystalline 
digestion-products  as  the  biuret  reaction  disappeared.  The 
peptones  which  are  formed  in  the  course  of  ordinary  diges- 
tion when  in  contact  with  the  living  intestinal  mucosa  there- 

1  Cohnheim:  Zeitschr.  f.  physiol.  Chemie,  1901,  XXXIII,  p.  451; 
1902,  XXXV,  p.  134. 

146 


ACTION  OF   THE  ENZYMES.  I  17 

fore  disappear,  not  because  they  are  synthesized  into  more 
complex  compounds,  but  because  they  are  broken  up  into 
simpler  ones.  A  recognition  of  this  fact  led  to  the  discov- 
ery of  protease  (erepsin),  to  a  discussion  of  the  identifica- 
tion and  properties  of  which  we  shall  now  turn. 

The  proof  that  the  change  from  peptone  to  the  simple 
crystalline  compounds  mentioned  above  occurs  under  the 
influence  of  a  ferment  contained  in  the  wall  of  the  small 
intestine  can  be  shown  very  well  by  introducing  into  each  of 
two  tubes  a  solution  of  peptones  and  several  pieces  of  well- 
washed  intestinal  mucous  membrane  from  a  freshly  killed  dog 
or  cat.  One  of  the  two  tubes  is  then  boiled,  after  which  both 
are  set  aside  in  an  incubator  at  39°  C.  for  a  number  of  hours. 
While  in  the  boiled  tube  the  biuret  reaction  persists  even  if  we 
wait  for  days  or  weeks,  it  is  found  to  become  fainter  and 
fainter  in  the  unboiled  tube,  until  in  the  course  of  perhaps  an 
hour  or  two — depending  upon  the  amount  of  peptone  and  in- 
testinal mucous  membrane  originally  present — the  biuret 
reaction  disappears  entirely.  Hand  in  hand  with  this  dis- 
appearance of  the  biuret  reaction  goes  an  increase  in  the 
amount  of  crystalline  precipitate  which  may  be  obtained 
upon  the  addition  of  suitable  reagents,  and  to  a  discussion  of 
which  we  shall  return  immediately. 

It  is  only  necessary  to  add  that  this  ferment,  which  the 
above  simple  experiment  has  indicated  exists  in  the  mucous 
membrane  of  the  intestine,  can  be  extracted  from  it.  Simple 
extraction  with  an  alkaline  physiological  salt  solution  of  the 
intestinal  mucous  membrane,  after  it  has  been  scraped  from 
the  submucosa  and  thoroughly  triturated  in  a  mortar  with 
sand,  suffices  to  yield  a  very  active  solution  of  the  enzyme, 
though,  of  course,  not  a  very  pure  one.  The  same  difficulties 
which  were  found  to  exist  in  the  preparation  of  the  other 
ferments  in  a  pure  state  exist  here  also.  By  fractional 
precipitation  with  ammonium  sulphate  much  purer  specimens 
of  the  ferment  may  be  obtained,  but  for  the  details  of  this 
process  the  reader  must  consult  the  original. 


148  PHYSIOLOGY  OF  ALIMENTATION. 

We  have  now  to  discuss  the  character  of  the  crystalline 
products  into  which  protease  splits  peptones.  If  a  protease 
solution  obtained  from  dog's  intestine,  for  example,,  is  added 
to  a  solution  of  peptones  (in  Kuhne's  sense),  and  the  whole 
is  kept  in  an  incubator  at  body  temperature,  it  is  found  that 
only  a  slight  biuret  reaction  is  obtained  on  the  third  or 
fourth  day  from  the  reaction  mixture  which  on  the  first  day 
gave  an  intense  reaction.  If,  now,  the  digestion  experiment 
is  continued  a  few  days  longer,  the  biuret  reaction  disappears 
entirely,  indicating  that  the  peptones  have  been  changed 
into  something  else.  This  "something  else"  has  been  shown 
to  consist  of  leucin,  tyrosin,  lysin,  histidin,  arginin,  and 
ammonia,  all  of  them  substances  therefore  identical,  quali- 
tatively at  least,  with  those  obtained  when  alkali-proteinase 
(trypsin)  is  allowed  to  act  on  a  protein.  The  question  may 
therefore  very  justly  be  raised,  Are  we  not  perhaps  really 
dealing  with  the  action  of  alkali-proteinase  in  an  extract  of 
the  small  intestine?  This  question  is  to  be  answered  in  the 
negative,  and  for  the  following  reasons.  Alkali-proteinase, 
it  is  well  known,  acts  upon  a  large  number  of  the  so-called 
"native"  proteins— for  example,  fibrin,  white  of  egg,  serum 
albumin,  etc.  If  proper  precautions  are  taken  to  obtain  a 
protease  solution  free  from  alkali-proteinase  this  property 
of  acting  on  native  proteins  is  lacking.  Fibrin,  for  example, 
which  is  acted  upon  so  rapidly  by  alkali-proteinase  that  it 
can  scarcely  be  used  in  quantitative  studies  with  this  fer- 
ment, may  remain  in  a  protease  solution  for  days,  even  if  the 
fibrin  has  not  been  boiled,  without  showing  any  evidences 
of  having  been  attacked. 

One  of  the  ordinary  "native"  proteins  is,  however,  acted 
upon  by  protease,  and  that  is  the  casein  of  milk.  This 
fact  is  of  physiological  importance,  as  the  presence  of  protease 
in  the  intestine  renders  one  of  the  foods  of  infants  capable 
of  digestion  even  when  the  ordinary  proteolytic  ferments 
(acid-  and  alkali-proteinase)  are  lacking.  Protease  will  act 
also  upon  certain  of  the  proteoses,  but  its  activity  manifests 


ACTION   OF   THE  ENZYMES.  1  10 

itself  par  excellence  upon  the  peptones.     As  the  proteoses 

constitute,  with  the  exception  already  given,  I  lie  chemically 
most  complex  substances  upon  which  Coiinheim's  ferment 
acts,  it  has  been  called  protease. 

Through  the  investigations  of  a  number  of  authors,  more 
especially  Vernon,1  we  have  become  acquainted  with  the 
presence  of  protease  in  other  tissues  besides  the  small  intes- 
tine. It  is  very  probable  that  this  fact  will  necessitate  a 
revision  in  our  knowledge  of  the  ultimate  digestion-products 
of  alkali-proteinase,  for  the  two  ferments  are  frequently 
present  in  the  same  tissues,  and  no  doubt  some  of  the  sub- 
stances which  are  to-day  believed  to  have  been  produced 
through  the  activity  of  the  alkali-proteinase  are  really  pro- 
duced through  the  protease  which  is  present  simultaneously 
and  which  has  not  been  considered  in  the  analyses  at  present 
at  hand.  Of  interest  also  in  this  connection  is  the  fact  that 
the  "  Bence-Jones  protein,"  which  appears  in  the  urine  in 
certain  pathological  states,  is  not  acted  upon  by  protease. 
This  seems  to  indicate  that  it  does  not  belong  to  the  pro- 
teoses (albumoses),  under  which  heading  it  is  usually  classi- 
fied. 

Protease,  like  other  ferments,  is  markedly  affected  by  the 
character  of  the  medium  in  which  it  is  active.  It  acts  best 
in  an  alkaline  medium,  although  it  is  still  able  to  bring  about 
its  characteristic  effects  in  one  having  an  acid  reaction. 

ii.  Lipase. — Under  the  term  lipase  (steapsin)  or  the 
lipases  we  understand  those  ferments  that  have  the  power 
of  acting  upon  neutral  fats  of  various  kinds  and  splitting 
these  into  their  constituent  fatty  acids  and  alcohols.  The 
earlier  investigators  believed  that  the  formation  of  an  emul- 
sion from  the  fat  represented  one  of  the  characteristic  prop- 
erties of  lipase.  This  is  not  true,  however.  The  distinguish- 
ing property  of  lipase  resides  in  its  power  of  bringing  about 
not  a  physical  but  a  chemical  change1  in  the  fat.     While  we 

1  Vernon:  Journal  of  Physiology,  1904,  XXXI 1 ,  p.  33. 


150  PHYSIOLOGY  OF  ALIMENTATION. 

are  to-day  acquainted  with  the  presence  of  lipase  in  a  large 
variety  of  plant-cells,  it  is  interesting  that  the  discovery  of 
lipase  was  originally  made  in  experiments  on  the  physiology 
of  the  pancreas.  This  organ  contains  large  quantities  of  the 
ferment,  but  it  is  well  to  remember  that  lipase  is  one  of  the 
most  widely  distributed  enzymes  in  the  animal  organism,  oc- 
curring in  practically  every  organ  of  the  mammal.  The  liver, 
the  stomach,  the  small  intestine,  the  kidneys,  the  subcuta- 
neous tissues,  the  mammary  glands,  the  blood,  and  the  lymph, 
all  contain  lipase. 

The  fats  of  greatest  physiological  importance  are  all  of 
them  esters  of  the  triatomic  alcohol  glycerine  with  palmitic, 
stearic,  or  oleic  acids.  These  fats  (known  as  palmitin,  stearin, 
and  olein)  take  up  water  under  the  influence  of  lipase  and 
split  into  glycerine  and  fatty  acid.  A  quantitative  deter- 
mination of  the  activity  of  a  lipase  may  therefore  be  made 
by  ascertaining  the  amount  of  acid  that  is  formed.  Quali- 
tatively the  formation  of  the  acid  can  be  readily  demon- 
strated by  the  addition  of  an  indicator  to  a  mixture  of  fat  and 
lipase. 

In  laboratory  studies  with  lipase,  palmitin,  stearin,  and 
olein  are  comparatively  little  used.  Other  esters  are  acted 
upon  more  rapidly  by  the  ferment,  so  that  this  property,  in 
addition  to  their  ready  solubility  in  water,  renders  them  more 
suitable  for  study.  In  this  way  monobutyrin,  ethyl  butyrate, 
etc.,  have  come  to  be  extensively  used. 

Pure  preparations  of  lipase  have  never  been  obtained. 
The  best  rapidly  lose  in  strength  in  the  course  of  a  few  days, 
even  when  most  carefully  protected.  Ordinarily,  simple 
aqueous  or  NaCl-solution  extracts  are  made  of  entirely  fresh 
organs  which  are  minced  and  ground  up  in  a  mortar  with 
quartz  sand.  These  extracts  are  then  used  for  experimental 
purposes.     Glycerine  extracts  have  also  been  prepared. 

Lipase  is,  in  the  presence  of  water,  exceedingly  sensitive 
to  comparatively  low  temperatures.  When  dry,  the  lipase 
from  the  castor-oil  bean  will  stand  a  temperature  above  100°  C, 


'  ACTIOS  OF   THE   ENZYMES.  L53 

for  some  time  without  injury,  according  to  Taylor's  obser- 
vations. The  presence  of  even  a  small  amount  of  water 
soon  makes  the  highest  temperature  that  this  lipase  can 
withstand  fall  far  below  the  boiling-point. 

Quantitative  studies  show7  that  the  activity  of  lipase  is  as 
dependent  upon  external  conditions  as  is  the  activity  of  other 
enzymes.  An  increase  in  the  concentration  of  the  lipase  in 
a  reaction  mixture  is  followed  by  an  increase  in  the  velocity 
of  the  cleavage  of  the  fat,  but  by  no  means  in  proportion  to 
the  amount  of  lipase  added. 

The  amount  of  fat  split  in  a  reaction  mixture  under  the 
influence  of  lipase  increases  with  the' time,  but  becomes  less 
in  each  succeeding  unit  of  time.  All  the  fat  is  never  split, 
even  when  infinite  time  is  allowed,  owing  to  the  fact  that 
the  activity  of  this  ferment  is  reversible. 

Lipase  is  exceedingly  sensitive  toward  acids,  losing  its 
activity,  for  example,  in  a  very  few  minutes  in  a  hydrochloric- 
acid  solution  having  the  concentration  of  the  acid  in  the 
stomach.  At  the  height  of  digestion  the  lipase  found  in  the 
stomach  can  therefore  have  but  little  or  no  effect  upon  the 
fats  of  the  food.  Lipase  acts  best  in  a  neutral  or  slightly 
alkaline  medium.  Its  activity  is  markedly  reduced  or  done 
away  with  entirely  through  the  presence  of  various  neutral 
salts. 

That  the  activity  of  lipase  is  reversible  was  demonstrated 
in  this  country  by  Kastle  and  Loevenhart,1  and  independ- 
ently of  them  by  Hanriot2  in  France.  Kastle  and  Loeven- 
hart were  able  to  show  that  if  lipase  is  added  to  ethyl  butyrate 
this  is  split  into  ethyl  alcohol  and  butyric  acid.  The  re- 
action is,  however,  incomplete.  If,  on  the  other  hand,  lipase 
is  added  to  a  mixture  of  ethyl  alcohol  and  butyric  acid,  ethyl 
butyrate  is  synthesized. 

This    may    be    illustrated   by    the    following    experiment: 

'Kastle  and  Loevenhart:  American  Chem.  Jour.,  1900,  XXIV, 
p.  191. 

2  Hanriot:  Compt.  rend.  Soc.  biol.,  1901,  LIU,  p.  70. 


152  PHYSIOLOGY  OF  ALIMENTATION. 

1000  c.c.  of  an  extract  of  ground  pancreas  were  mixed  with 
1900  c.c.  of  a  1/10  normal  butyric-acid  solution  and  100  c.c. 
of  95  percent  alcohol.  To  the  mixture  was  added  some 
thymol  to  prevent  the  development  of  bacteria,  and  the 
whole  was  kept  for  40  hours  at  a  temperature  of  23°  to  27°  C. 
A  similar  mixture  was  prepared  as  a  control,  only  the  pan- 
creatic extract  was  boiled  before  being  mixed  with  the 
butyric  acid  and  alcohol.  At  the  conclusion  of  the  experi- 
ment 25  c.c.  were  distilled  over  from  each  of  the  flasks. 
Had  any  ethyl  butyrate  been  synthesized  from  the  butyric 
acid  and  alcohol  this  distillate  ought  to  contain  it.  It  was 
found  that  the  distillate  from  the  first  flask,  containing  the 
unboiled  pancreatic  extract,  smelled  strongly  of  ethyl  butyrate, 
and  after  being  further  purified  rendered  water  milky  when 
poured  into  it,  owing  to  the  formation  of  the  only  partially 
soluble  ethyl  butyrate  droplets;  it  formed  a  soap  (sodium 
butyrate)  upon  the  addition  of  NaOH,  and  yielded  butyric 
acid  when  digested  with  lipase.  The  distillate  from  the  flask 
containing  the  boiled  pancreatic  extract  smelled  of  butyric 
acid,  gave  no  turbidity  when  poured  into  water,  and  was  un- 
changed through  the  addition  of  lipase.  A  synthesis  of 
ethyl  butyrate  from  butyric  acid  and  alcohol  under  the  in- 
fluence of  a  substance  contained  in  the  pancreas  and  de- 
stroyed by  heating— in  other  words,  the  synthesis  of  an 
ester  under  the  influence  of  lipase — seems  proved  by  this 
experiment. 

Just  as  in  the  analysis  of  an  ester  (or  fat)  the  reaction  is 
incomplete,  so,  too,  is  the  synthesis.  Before  all  the  butyric 
acid  and  alcohol  have  been  built  up  into  ethyl  butyrate,  the 
reaction  comes  to  a  standstill  (practically  speaking).  We 
are  in  this  case  also  dealing  with  a  reversible  reaction  cata- 
lyzed by  a  ferment.  The  lipase  acts  just  as  the  maltase  did 
in  the  case  of  maltose  and  glucose — it  only  hastens  the  estab- 
lishment of  an  equilibrium  between  the  fat  (ethyl  butyrate 
in  this  case),  on  the  one  hand,  and  fatty  acid  and  alcohol,  on 
the  other.     Whether  lipase  will  have  an  analytic  or  a  syn- 


ACTION  OF   THE  ENZYMES.  153 

thetie  action  upon  any  mixture  of  fat,  fatty  acid,  and  alcohol 
is  dependent  solely  upon  the  relative  amounts  of  these  sub- 
stances present.  Speaking  broadly,  the  lipase  will  analyze 
fat  whenever  this  substance  is  present  in  excess,  while  it  will 
synthesize  it  if  the  fatty  acid  and  alcohol  are  in  excess,  and 
it  will  do  one  or  the  other  of  these  until  equilibrium  has  been 
established. 

Hanriot  worked  not  with  ethyl  buytrate  but  with  mono- 
butyrin,  which  under  the  influence  of  lipase  is  split  into 
glycerine  and  butyric  acid.  When,  under  proper  external 
conditions,  lipase  is  added  to  a  mixture  of  glycerine  and 
butyric  acid,  monobutyrin  is  produced,  as  Hanriot  was 
able  to  show  by  isolation  of  that  compound. 

The  synthesis  of  chemically  much  more  complicated  esters 
than  ethyl  butyrate  can,  however,  be  brought  about  through 
lipase.  With  the  lipase  obtained  from  the  castor-bean 
Taylor  *  succeeded  in  synthesizing  triolein  from  a  mixture  of  . 
oleic  acid  and  glycerine.  Since  this  same  ferment  is  un- 
able to  split  triolein  and  other  fats  completely,  the  reaction 
coming  to  a  standstill  when  some  75  to  90  percent  of  the 
original  fat  has  been  broken  up  into  glycerine  and  oleic  acid, 
the  conclusion  seems  to  be  justified  that  the  lipase  obtained 
from  this  source  is  also  able  to  catalyze  both  the  analysis  and 
the  synthesis  of  fats  in  a  way  similar  to  that  described  in 
Kastle  and  Loevenhart's  experiments. 

12.  Sucrase  (invertase,  invertin)  is  a  ferment  which  is  I 
characterized  by  its  power  of  splitting  the  disaccharide,  cane= 
an  p.  r  fsijernsM  into  a  mivfip-n  of  two  monosaccharides^  The 
monosaccharides  produced  are  known  as  "iuxGLt=£li£^r," 
and  consist  of  a  mixture  of  equal  parts  of  dextrose  and  hriVU- 
lose.  The  change  which  cane-sugar  undergoes  under  the 
influence  of  sucrase  is  expressed  by  the  following  formula: 

C12H22O11  +HoO  =  CfiHi206  +CI1il>(  V, 

Sucrose  Water  Dextrose  Ltevulose 

'Taylor:  University  of  California  Publications,  Pathology,  1904, 
I,  p.  33. 


154  PHYSIOLOGY  OF   ALIMENTATION. 

Sucrase  is  found  widely  distributed  throughout  the  vege- 
table kingdom.  In  animal  physiology  it  finds  its  importance 
as  a  constituent  of  the  intestinal  juice.  Its  presence  has  also 
been  claimed  in  the  secretions  of  the  mouth  and  stomach. 
In  the  former  of  these  sucrase  is  probably  not  present  as  a 
constituent  of  the  saliva  itself,  but  is  to  be  looked  upon  rather 
as  a  contamination  due  to  the  excretion  of  this  ferment  by 
some  of  the  bacteria  which  are  constantly  present  in  the 
t  buccal  cavity.  The  view  that  bacteria  are  the  source  of  the 
'  sucrase  of  the  stomach  is  probably  also  correct.  Some  of  the 
authors  who  have  concluded  that  sucrase  is  present  in  the 
pure  secretion  of  the  stomach,  simply  because  the  gastric 
juice  has  the  power  of  inverting  cane-sugar,  have  overlooked 

Ithe  fact  that  the  hydrochloric  acid  has  this  power  by  itself. 
In  foot  most  of  the  invert-sugar  which  is  found  in  the  stomach 
after  a  meal  of  cane-sugar  is  attributable  to  the  action  of, 
the  hydrochloric  acidj.  Most  of  the  cane-sugar  which  enters 
the  alimentary  tract  seems  to  remain  unaltered,  however, 
until  it  comes  in  contact  with  the  juices  of  the  small  intestine. 
^  For  study  sucrase  is  usually  obtained  from  ypa.st^  a.  pnlt^rp 
of  asper^illns.  or  sorrm  nthw  vpo^to^jp  r>Qj]  The  method 
of  Duclaux,  which  probably  yields  the  most  active  prepara- 
tions of  the  enzyme,  consists  in  growing  aspergillus  upon  a 
nutrient  fluid  for  several  days,  and  later  substituting  a  solu- 
tion of  cane-sugar  for  the  nutrient  fluid.  After  growing  upon 
this  for  about  three  more  days,  the  mould  gives  off  its  sucrase 
to  the  solution.  The  whole  is  then  filtered,  and  the  filtrate 
vhich  represents  a  solution  of  sucrase  is  used  for  the  purposes 
iesired.  It  is  also  possible  to  obtain  sucrase  in  a  dry  but  less 
active  state  by  the  method  of  Denathe.  Yeast,  after  being 
kept  under  absolute  alcohol  for  a  time,  is  dried,  pulverized, 
and  extracted  with  water.  After  filtering,  ether  is  added 
to  the  filtrate  and  the  whole  shaken.  A  gummy  mass  sepa- 
rates, which  is  dissolved  in  distilled  water,  and  this  solution  is 
added  drop  by  drop  to  absolute  alcohol.  The  powdered  pre- 
cipitate obtained  in  this  way  is  separated  by  filtration  and 


ACTION  OF  THE  ENZYMES.  155 

dried.  The  resulting  while  powder  keeps  for  a  long  time, 
and  when  dissolved  in  water  shows  great  diastatic  ac- 
tivity.1 

The  inversion  of  cane-sugar  as  catalyzed  by  sucrase  is 
markedly  influenced  by  time,  concentration  of  the  ferment, 
temperature,  and  other  external  conditions.  In  infinite  time 
a  small  amount  of  the  ferment  brings  about  as  much  change 
as  a  larger  amount.  If  the  products  of  the  reaction  (dextrose 
and  lsevulose)  are  not  removed,  the  reaction  is  incomplete, 
and  when  the  catalysis  has  come  to  a  standstill  all  three  sub- 
stances are  present  in  the  reaction  mixture.  It  is  ordinarily 
said  that  the  products  of  the  reaction  interfere  with  the  action 
of  the  enzyme — a  fact  which  we  have  learned  before  in  the 
consideration  of  most  of  the  other  ferments.  The  catalysis 
of  the  cane-sugar  under  the  influence  of  sucrase,  and  the 
catalysis  of  the  same  substance  under  the  influence  of  acids — 
which  bring  about  the  same  chemical  change  in  the  sucrose — 
differ  in  this  regard,  for  no  limit  is  reached  when  acids  are 
employed,  the  inversion  being  in  this  case  complete. 

Only  when  the  concentration  of  the  ferment  is  high,  the 
temperature  low,  and  the  experiment  continued  for  but  a 
short  time  does  an  almost  constant  relation  exist  between 
the  concentration  of  the  ferment  and  the  amount  of  invert- 
sugar  formed.  This  explains,  for  example,  the  results  of 
O'SuLLivANandToMPSON,  who  believed  that  the  catalysis  of 
cane-sugar  under  the  influence  of  sucrase  was  governed  by 
the  same  laws  as  the  catalysis  under  the  influence  of  acids. 
In  every  experiment  which  is  continued  a  sufficient  length 
of  time,  the  amount  of  invert-sugar  formed  in  the  unit  of 
time  from  the  sucrose  in  the  presence  of  sucrase  gradually 
diminishes.  The  point  at  which  the  reaction  comes  to  a 
standstill  varies  with  external  conditions  of  temperature, 
concentration  of  the  reaction  mixture,  etc.     But  only  when 

1  See  Effront:  Die  Diastasen.    Translated  into  German  l>y  BttCH- 

eler,  Leipzig,  l'JUO,  I,  p.  5U. 


156  PHYSIOLOGY  OF  ALIMENTATION. 

the  products  of  the  inversion  are  removed  does  the  catalysis 
go  to  an  end. 

The  optimal  temperature  for  sucrase  is  given  by  Kjeldahl 
as  52°  C.  for  a  preparation  obtained  from  yeast.  Effront 
states  that  at  0°  C.  the  activity  of  sucrase  is  practically  nil, 
rises  slowly  up  to  30°  C.  to  increase  more  rapidly  up  to  50°  C, 
after  which  it  falls  again.  At  a  temperature  of  65°  C.  the 
ferment  is  rapidly  destroyed.  External  conditions  modify 
very  markedly  the  points  at  which  the  optimal  temperature 
and  the  maximal  temperature  are  attained.1  While  a  dilute 
solution  of  sucrase  may  be  kept  at  52°  C.  for  an  hour  without 
losing  its  fermentative  activity,  more  concentrated  solutions 
suffer  considerably  if  kept  at  the  same  temperature  for  even 
shorter  periods  of  time.  At  65°  C.  a  concentrated  solution 
of  sucrase  is  entirely  destroyed  within  an  hour,  while  a  more 
dilute  solution  bears  this  treatment  with  only  a  partial  loss 
of  its  activity.  Besides  these  variations  in  optimal  and  maxi- 
mal temperatures  in  the  same  preparation  of  sucrase  under 
different  external  conditions,  marked  differences  are  also 
found  between  sucrase  preparations  obtained  from  different 
sources.  The  various  sucrase  preparations  differ,  for  example, 
in  their  optimal  and  maximal  temperatures,  in  their  resistance 
to  chemical  and  physical  agents,  etc.  On  this  ground  certain 
investigators  have  tried  to  establish  the  existence  of  varieties 
of  sucrase.  The  same  can  be  said  of  this  ferment,  however, 
which  has  been  said  of  others,  that  when  obtained  from  dif- 
ferent sources  the  impurities  accompanying  the  preparations 
are  not  the  same.  Preparations  of  sucrase  differ,  therefore, 
not  because  of  specific  differences  in  the  sucrase  itself,  but 
because  of  specific  differences  in  the  impurities  accompanying 
the  sucrase.  Certain  of  these  act  more  deleteriously  upon  the 
enzyme  than  others,  and  we  get  in  consequence  the  long  line 
of  differences  which  authors  have  claimed  exist  in  the  sucrases 
themselves. 

1  By  maximal  temperature  is  meant  the  temperature  at  which  the 
fermentative  reaction  no  longer  takes  place. 


ACTIOS  OF   THE  ENZYMES.  107 

It  has  been  shown  by  Kjeldahl  that  sucrase  acts  best  in  a 
slightly  acid  medium.  A  greater  concentration  of  the  acid, 
be  it  inorganic  or  organic,  acts  deleteriously,  ns  does  also  an 
alkali  in  any  concentration.  In  fact  the  activity  of  sucrase 
is  markedly  influenced  by  a  concentration  of  alkali,  the  pres- 
ence of  which  cannot  even  be  recognized  by  our  ordinary 
indicators.  As  the  intestinal  juice  is  neutral  or  if  anything 
slightly  acid,  we  see  that  sucrase  acts,  so  far  as  reaction  is 
concerned,  under  favorable  conditions  in  the  body. 

13.  Lactase  is  a  ferment  which  has  the  power  of  acting 
upon  the  disaccharide  lactose  (milk-sugar)  and  converting  it 
into  the  monosaccharides  d-glucose  (dextrose)  and  d-galac- 
tose. 

C12H22O11 +H2O  =CeHi206  +C6H12O6. 

Lactose  Water        Dextrose  Galactose 

Various  yeasts  usually  serve  as  a  source  of  the  ferment  which 
has  been  studied  more  particularly  by  Beyerinck,1  Emil 
Fischer,2  Armstrong,3  and  Weinland.4  Emil  Fischer  ob- 
tained the  ferment  most  readily  by  making  an  aqueous  ex- 
tract of  Saccharomyces  Kefir  and  precipitating  the  ferment 
with  alcohol.  The  reversible  activity  of  this  enzyme  has 
been  demonstrated  by  Emil  Fischer  and  Armstrong,  who 
found  that  milk-sugar  (or  at  least  a  disaccharide  closely  re- 
lated to  it)  appears  in  a  concentrated  mixture  of  d-glucose 
and  d-galactose  under  the  influence  of  lactase,  when  the 
whole  is  kept  in  a  thermostat  at  35°  C. 

The  fact  that  milk-sugar  is  one  of  the  commonest  constitu- 
'  nts  of  our  food,  especially  in  suckling  animals,  gives  the 
occurrence  of  lactase  in  certain  organs  its  physiological  im- 
portance.    The  exceedingly  contradictory  statements  of  dif- 

1  Beyerinck:  Contrail)!,  f.  Bacterid.,  1889,  VI,  p.  II. 

2  Emil  Fischer:  Berichte  d.  deut.  chem.  Gesellsch.,  L894,  XXVII, 
3481. 

3  Emil,  Fischer  and  Armstrong:  Berichte  d.  deut.  chem.  Gesellsch. 
1902,  XXXV,  |>.  3144. 

4  Weinland:  Zeitschr.  f.  Biol.,  1899,  XXXVIII, p.  606. 


158  PHYSIOLOGY  OF  ALIMENTATION. 

ferent  investigators  regarding  the  presence  or  absence  of 
lactase  in  different  organs  and  secretions  of  the  alimentary 
tract  have  been  harmonized  by  the  careful  experiments  of 
Weinland.  There  seems  to  be  no  question  but  that  lactase 
is  present  in  the  secretions  and  mucous  membrane  of  the  small 
intestine  of  all  suckling  animals  and  in  certain  adult  animals, 
provided  they  are  fed  milk-sugar  or  a  food  containing  it. 
The  same  holds  true  of  the  pancreas.  Sucklings  secrete 
lactase  in  their  pancreatic  juice,  and  the  gland  contains 
the  enzyme.  Adult  animals  come  to  have  lactase  present  in 
their  pancreas  if  they  are  fed  milk-sugar.1 

14.  Arginase. — Under  this  heading  Kossel  and  Dakin2 
have  described  a  ferment  which  has  the  interesting  property 
of  acting  upon  arginin  and  splitting  this  into  the  chemically 
much  simpler  ornithin  and  urea.  The  ferment  is  widely 
distributed  throughout  the  body,  though  it  is  present  in 
different  amounts  in  the  various  organs.  The  liver  probably 
contains  the  largest  amount,  while  next  in  order  come  the 
kidneys,  spleen,  and  intestinal  mucous  membrane. 

Arginase  can  be  readily  obtained  by  extracting  any  of  the 
organs  named  with  water  and  dilute  acetic  acid,  but,  as  with 
other  ferments,  only  a  small  portion  of  the  ferment  actually 
present  within  the  tissues  can  be  gotten  out.  Absolutely 
pure  arginase  has  not  as  yet  been  prepared,  but  advantage 
can  be  taken  of  the  fact  that  it  is  readily  precipitated  by 
ammonium  sulphate,  and  alcohol  and  ether  to  free  it  from 
many  of  the  impurities  which  accompany  the  ordinary  acetic- 
acid  extract. 

Some  idea  of  the  readiness  with  which  arginase  acts  upon 
arginin  can  be  obtained  from  the  following  experiments ,  in 
which  are  indicated  the  amounts  of  this  substance  which 
may  be  split  in  ten  minutes  by  an  extract  made  from  25 
gms.  of  liver  substance.     In  one  experiment  2.7  gms.  of  the 

1  See  Chapter  XII..  Part  7. 

2  Kossel  and  Dakin:  Zeitschrift  fur  physiol.  Chemie,  1904,  XLI,  p. 
341,  and  XLII,  p.  183. 


ACTION  OF   THE   ENZYMES.  I  5'.) 

original  3.2  gms.  of  arginin  that  were  Added  to  such  an 
extract,  were  split,  2.0  gins,  of  ornithin  and  1.1  gms.  of  urea 
being  recovered  from  the  reaction  mixture.  In  another 
experiment  3.3  gms.  of  arginin  of  the  original  3.6  gms. 
added  were  split,  2.7  gms.  ornithin  and  1.2  gms.  urea  being 
recovered. 

These  experiments  furnish  an  interesting  example  of  the 
apparent  ease  with  which  chemical  changes  are  brought 
about  in  a  living  organism,  which  in  vitro  cannot  often  be 
accomplished  without  resort  to  what  may  be  termed  coarse 
chemical  procedures.  The  ease  with  which  arginase  splits 
arginin  into  ornithin  and  urea  stands  in  sharp  contrast  to 
the  difficulty  with  which  this  same  chemical  change  is  brought 
about  under  the  influence  of  boiling  mineral  acids. 

The  experiments  of  Kossel  and  Dakin  give  us  an  insight 
into  the  means  by  which  urea  is  produced  in  the  liver  and 
various  other  organs  of  the  body.  Whether  the  urea  which 
was  found  by  Claude  Bernard  and  others  in  the  secretions 
of  the  intestine  is  dependent  upon  the  presence  of  this  en- 
zyme in  the  wall  of  the  gut,  or  whether  we  have  in  addition 
a  true  excretion  of  this  substance  by  the  intestinal  canal, 
cannot  be  settled  until  further  experiments  have  been  made.1 

See  Chapter  XVIII.  Part  1. 


CHAPTER  IX. 

THE  BACTERIA  OF  THE  ALIMENTARY  TRACT. 

A  discussion  of  the  bacteria  of  the  alimentary  tract  fol- 
lows very  naturally  upon  a  discussion  of  the  enzymes  elab- 
orated here,  for  the  various  bacteria  contain  enzymes  in 
their  bodies  and  secrete  them.  Some  of  these  bacterial  en- 
zymes are  not  unlike  those  which  are  secreted  by  the  glands 
of  the  alimentary  tract.  By  virtue  of  these,  the  bacteria  may 
therefore  augment,  in  a  limited  way,  the  activities  of  the 
alimentary  secretions.  In  large  part,  however,  the  bac- 
terial ferments  are  able  to  bring  about  changes  in  the  ali- 
mentary contents  which  differ  totally  from  those  brought 
about  by  the  secretions  of  the  alimentary  tract  proper.  The 
substances  formed  in  this  way  are  usually  harmless  in  char- 
acter, though  at  times,  through  excessive  production  or 
through  the  formation  of  specific  poisonous  substances,  they 
assume  even  a  pathological  importance. 

The  subject  of  the  bacteria  of  the  alimentary  tract,  to- 
gether with  a  discussion  of  their  physiological  and  patho- 
logical role,  has  given  rise  to  a  literature  which  is  simply 
enormous.  Nor  do  the  conclusions  reached  by  the  various 
authors  at  all  harmonize — a  fact  not  strange  when  the  com- 
plexity of  the  problem  is  recognized.  For  under  normal 
and  abnormal  conditions  practically  every  form  of  bacterium 
enters  the  intestinal  tract,  and  when  it  is  remembered  that 
usually  more  than  one  kind  of  micro-organism  is  present  at 
the  same  time,  that  the  medium  upon  which  they  grow  (food, 
etc.)  is  subject  to  the  greatest  variation,  and  that  the  agencies 

160 


THE  BACTERIA   OF    THE  ALIMENTARY  TRACT.     101 

active  in  inhibiting  their  growth  and  reproduction  arc  prac- 
tically not  at  all  understood,  it  is  not  strange  that  opinions 
differ. 

1.  That  bacteria  exist  throughout  the  alimentary  tract  is 
no  longer  doubted  by  any  one.  At  what  time  do  these  bac- 
teria appear?  The  majority  of  investigators  are  agreed  that 
under  normal  circumstances  the  alimentary  traot  of  new-born 
animals  is  sterile.  This  condition  of  affairs  does  not  last 
long,  however,  for,  as  shown  by  the  observations  of  Popoff, 
Schild,  and  Escherich,  the  faeces  of  young  children  may  con- 
tain several  kinds  of  bacteria  as  early  as  ten  hours  after  birth, 
and  only  rarely  are  they  absent  at  the  end  of  twenty-four. 
Bordano  found  even  the  colon  bacillus  thirteen  hours  after 
birth.  These  bacteria  enter  the  intestinal  tract  through 
air,  food,  and  bath-water  by  way  of  the  mouth  and  rectum.1 

2.  In  order  to  show  the  enormous  number  of  bacteria 
which  inhabit  the  intestinal  tract,  the  figures  of  Sucksdorff2 
may  be  cited,  who  found  in  one  milligram  of  normal  human 
faecal  matter  an  average  of  381,000  micro-organisms.  Yet 
the  figures  vary  considerably,  even  within  twenty-four  hours, 
between  the  extremes  of  2,300,000  and  25,000  per  milligram. 
The  variation  in  the  number  is,  according  to  Sucksdorff,  de- 
termined chiefly  by  the  kind  of  food,  and  but  little  by  the  total 
amount  of  fseces  or  the  amount  of  water  contained  in  them. 
When  only  sterile  food  is  consumed,  the  average  number  of 
bacteria  per  milligram  is  markedly  reduced.  Brotzu3  has 
observed  that  this  is  true  for  the  dog  also  when  fed  onty 
sterile  food.  From  the  total  amount  of  faeces  cast  off  and  the 
number  of  micro-organisms  contained  in  each  milligram,  the 

1  See,  for  example,  J.  H.  F.  Kohlbuugge:  Centralbl.  f.  Bakt.,  1001, 
XXX,  lte  Abth.,  p.  17;  Gerhardt:  Ergebnisse  der  Physiologic,  L904, 

111  lte  Abth.,  p.  107,  where  extensive  references  to  the  literature  may 
be  found. 

2  Sucksdorff:  Arch.  f.  Ilyg.,  1886. 

3  Quoted  from  Kohlbuuggi::  Centralbl.  f.  Bakt.,  1901,  XXX,  lte 
Abth.,  p.  13. 


162  PHYSIOLOGY  OF  ALIMENTATION. 

total  number  of  bacteria  voided  in  twenty-four  hours  can  be 
calculated.  For  this  figure  Gilbert  and  Dominici  give  as  an 
average  12,000  to  15,000  millions;  Sucksdorff  55,000  millions; 
Klein,1  who  probably  used  the  best  technique  of  the  three, 
8,800,000  millions. 

3.  The  weight  of  the  bacteria  excreted  in  twenty-four  hours 
has  been  calculated  by  Kleyn,2  who  estimates  that  1.13  per- 
cent of  the  dry  faeces  is  made  up  of  micro-organisms  and  that 
about  293  milligrams  are  cast  off  in  twenty-four  hours. 

4.  As  to  the  kinds  of  bacteria  inhabiting  the  alimentary 
tract,  the  following  may  be  said.  We  must  distinguish  first 
of  all  between  those  bacteria  which  are  almost  constantly 
present  in  the  digestive  tube  and  those  which  are  present 
only  under  certain  circumstances.  Under  the  latter  head- 
ing we  can  say  that  practically  every  known  form  of  micro- 
organism has  been  found  in  some  portion  of  the  intestinal 
tract  at  some  time.  A  large  number  of  saprophytic  bacteria 
are  always  found  in  the  mouth.  After  inhaling  the  air  of 
rooms  in  which  infectious  diseases  have  been  housed,  the 
bacteria  characteristic  of  that  disease  have  been  recovered 
from  the  mucous  membranes  of  the  mouth,  throat,  and  nose 
of  those  who  have  lived  in  these  rooms.  But  even  from 
the  noses  and  mouths  of  persons  following  the  ordinary  rou- 
tine of  life  have  virulent  pathogenic  bacteria  been  culti- 
vated. This  has  been  done  repeatedly  for  the  ordinary  pus 
organisms,  and  Noble  W.  Jones  has  shown  that  virulent 
tubercle  bacilli  are  not  uncommon  inhabitants  of  these  regions. 
For  the  most  part  these,  even  pathogenic,  bacteria  are  of 
little  or  no  importance.  When,  however,  the  health  of  the 
individual  as  a  whole,  or  the  resistance,  as  we  are  pleased 
to  call  it,  of  the  tissues  inhabited  by  these  micro-organisms 
is  reduced  through  any  cause  whatsoever,  they  are  able  to 
produce  their  characteristic  pathological  effects. 

The  oesophagus  harbors  practically  the  same  bacteria  that 

1  Klein:  Centralbl.  f.  Bakt.,  1899,  XXV,  p.  278. 

2  Kleyn:  Cited  from  Kohlbrtjgge,  1.  c. 


'nil-    IIACTKUIA   OF   Till:    M./MK.XTARY    TRACT.      163 

are  Found  in  the  mouth,  as  the  inhabitants  of  this  region  are 
simply  carried  through  this  tube  by  the  swallowed  saliva  and 
food.  In  the  stomach  (lie  number  of  bacteria  is  greatly  re- 
duced, :i  large  number  of  them,  as  will  be  shown  later,  being 
destroyed  by  (he  gastric  juice.  Yet  by  no  means  all  of  them 
arc  destroyed,  the  spore-bearing  varieties  being  especially 
successful  in  withstanding  (he  action  of  (he  gastric  juice. 
Yet  the  oilier  varieties — such  as  the  ordinary  pus  bacteria — 
can  also  traverse  the  stomach  without  losing  their  pathogenic 
properties.  It  is  certain  that  some  at  least  of  the  majority 
of  1  he  bacteria  found  in  the  mouth  can  pass  the  stomach  and 
be  carried  through  the  entire  intestine  uninjured,  for  Miller1 
was  able  to  isolate  from  the  stools  12  of  25  different  varieties 
which  he  had  recognized  in  the  mouth. 

Only  few  varieties  of  bacteria  are  found  throughout  the 
small  intestine.  As  the  caecum  is  approached,  however, 
their  number  increases  somewhat,  to  approach  a  maximum 
in  the  ascending  colon.  From  here  to  the  rectum  the  sep- 
arate varieties  change  but  little. 

Though  the  last  experiments  have  not  yet  been  made  in 
this  field  it  seems  fairly  certain  that  most  of  the  strict  anae- 
robes are  never  found  anywhere  in  the  alimentary  tract  after 
the  stomach  is  passed.  Of  the  varieties  of  bacteria  which  are 
found  we  will  not  mention  those  which  are  recognized  as  the 
cause  of  certain  primary  diseases,  nor  those  which  may  be 
found,  but  only  those  which,  generally  speaking,  arc  almost 
always  present.  Of  these  the  following  are  the  most  im- 
portant. 

As  a  constant  inhabitant  of  (he  upper  portions  of  the  small 
intestine  of  sucklings  Escherich  has  found  the  Bacterium 
lactis  acrogenes,  which  is  able  to  exist  here  because  of  its  power 
of  splitting  up  the  milk-sugar  of  the  food,  from  which  it  obtains 
its  necessary  supply  of  oxygen.  Corresponding  with  the 
ever-diminishing  amount  of  milk-sugar  in  (he  intestine  from 

1  Miller:   Deutsche  med.  VVochenschr.,  L885,  p.  843, 


164  PHYSIOLOGY  OF  ALIMENTATION. 

above  downwards  it  is  found  that  the  number  of  bacteria 
of  this  variety  also  decreases.  As  another  constant  inhabi- 
tant of  the  alimentary  tract  beyond  the  stomach  we  have  the 
Bacillus  coli  communis,  which  according  to  Escherich  first 
appears  in  small  numbers  high  up  in  the  small  intestine. 
From  here  the  number  of  bacteria  of  this  variety  increases 
progressively  from  above  downwards.  Kohlbrugge  ques- 
tions the  presence  of  the  Bacillus  coli  communis  in  any  por- 
tion of  the  small  intestine  except  the  region  near  the  ileocsecal 
valve.  The  csecum  is  considered  by  the  last-named  author 
as  the  distributing  depot  of  the  colon  bacillus,  from  which  it 
is  supposed  to  be  carried  outward  toward  the  rectum.  By 
the  term  colon  bacillus  are  here  understood  all  the  different 
varieties  of  this  micro-organism  which  have  been  described. 

The  two  above-mentioned  bacteria  were  for  a  long  time 
held  to  be  the  only  constant  inhabitants  of  the  intestinal  canal. 
Since  Escherich's  early  work  we  have  become  acquainted, 
however,  with  a  number  of  others  which  seem  to  be  constant 
inhabitants  of  the  large  bowel,  and  the  cause  here  of  certain 
of  the  putrefactive  changes  which  occur  in  this  region  of  the 
intestinal  tract  and  not  above  it.  Under  this  heading  belong 
the  Bacillus  putrificus,  certain  members  of  the  Proteus  group, 
and  bacteria  very  similar  to  the  Bacillus  subtilis.  The  first 
of  these  is  an  anaerobe  and  the  cause  of  the  bacterial  decom- 
position of  the  proteins  of  the  food.  The  products  of  this 
decomposition  give  the  faeces  their  odor.  The  absence,  as 
a  rule,  of  the  Bacillus  putrificus  from  the  intestine  above  the 
ileocsecal  valve  in  the  adult  explains  why  the  contents  of 
the  small  intestine  are  without  odor.  The  faeces  of  children 
are  also  free  from  odor  because  their  intestinal  tracts  nowhere 
harbor  this  bacillus.  Mention  must  also  be  made  of  the  Ba- 
cillus acidophilus,  an  acid-producing  organism  which,  like  the 
colon  bacillus,  may  at  times  be  pathogenic,  at  times  harmless.1 

1  Escherich,  Kohlbrugge,  etc.:  Centralbl.  f.  Bakt.,  etc.,  1901, 
XXX,  lteAbth.,p,73. 


THE   BACTERIA   OE   THE  ALIMENTARY   TRACT.     L65 

As  more  or  less  constant  inhabitants  of  various  portions  of 
the  intestinal  tract  have  also  been  described  certain  spirilli 
and  blastomyces  (yeasts)  as  also  moulds  and  streptobacilli. 
The  majority  of  these  are  harmless  saprophytes.  It  must 
also  be  mentioned  in  this  connection  that  it  is  probable  that 
the  faeces  contain  bacteria  which  it  has  not  as  yet  been  pos- 
sible to  cultivate  on  artificial  media. 

5.  The  following  may  be  said  regarding  the  distribution 
of  the  bacteria  in  the  alimentary  tract.  The  mouth  has  an 
exceedingly  plentiful  bacterial  flora  which  through  the 
agency  of  the  food  and  swallowed  saliva  is  carried  down 
the  oesophagus.  In  the  stomach  the  bacteria  become  greatly 
reduced  in  number.  This  is  dependent  upon  the  fact  that 
the  secretions  of  the  gastric  mucosa  destroy  or  at  least 
inhibit  the  growth  of  micro-organisms  in  this  organ.  Which 
constituent  of  the  gastric  juice  it  is  that  brings  about  this 
sterilization  in  the  stomach  is  not  entirely  decided,  but  it 
seems  to  be  the  hydrochloric  acid.  The  pepsin  by  itself 
has  no  apparent  action  upon  the  bacteria  and  simple  hydro- 
chloric-acid solutions  of  the  concentration  found  in  the 
stomach  are  sufficient  to  bring  about  the  same  degree  of 
bacterial  destruction  as  is  brought  about  by  the  gastric  juice. 

The  bactericidal  effect  of  the  gastric  juice  is  of  no  mean 
( linical  importance,  for,  as  has  been  shown  by  Oppler,  Sei- 
fkrt,  M ester,  and  others,  gastric  and  intestinal  fermentation 
is  much  greater  in  cases  of  anacidity  of  the  stomach  than 
under  normal  circumstances.  Oppler  believes  that  many 
chronic  diarrhoeas  are  primarily  dependent  upon  a  lack  of 
acid  in  the  stomach,  and  Mester  has  found  that  while  in- 
testinal putrefaction  is  not  increased  when  putrid  meat 
is  fed  to  healthy  dogs,  this  is  the  case  when  anacidity  is 
present.  To  the  decreased  amount  or  total  lack  of  hydro- 
chloric acid  is  also  attributable  the  presence  of  butyric  and 
other  fatty  acids  in  the  stomach  contents  of  patients  suffer- 
ing from  gastric  carcinoma  and  other  diseases  of  t  lie  stomach. 
These  acids  are  produced   in  part  through   the  deeomposi- 


166  PHYSIOLOGY  OF  ALIMENTATION. 

tion  of  the  fatty  constituents  of  the  food  by  certain  bacteria 
which  are  killed  when  the  secretions  from  the  gastric  mucous 
membrane  are  normal,  in  part  through  the  action  of  the 
lipase  normally  present  in  the  gastric  secretion,  which  in 
the  absence  of  hydrochloric  acid  can  exhibit  its  character- 
istic activity. 

Throughout  the  duodenum,  jejunum,  and  ileum  bacteria 
are  exceedingly  scarce,  dependent  also  it  seems  upon  a 
deleterious  action  of  the  secretions  of  these  portions  of  the 
alimentary  tract  upon  the  bacteria.  It  is  entirely  probable 
that  the  scant  bacterial  development  found  in  these  locali- 
ties is  determined  chiefly  by  the  fact  that  the  alimentary 
contents  are  neutral  or  faintly  acid  in  reaction.  The  pres- 
ence of  even  traces  of  free  acids  inhibits  the  growth  of  most 
bacteria  very  markedly.  It  must  be  remembered  also  that 
the  food  passes  through  the  small  intestine  fairly  rapidly, 
so  that  little  time  is  allowed  for  bacterial  growth. 

The  pancreatic  juice  does  not  seem  to  have  any  bac- 
tericidal action.  Duclaux  found  bacteria  as  constant  inhab- 
itants of  the  pancreatic  duct,  where  they  are  bathed  in  the 
secretions  from  the  gland.  They  also  develop  readily  on 
macerated  pancreas.  It  is  of  interest  after  what  has  been 
said  above  that  the  pancreatic  juice  is  alkaline  in  reaction. 

Nor  has  the  bile  any  great  antiseptic,  action,  for  accord- 
ing to  Talma  even  but  slightly  virulent  colon  bacilli  can 
produce  a  severe  inflammation  of  the  liver  when  injected 
into  the  gall-bladder.  Whether  the  pancreatic  and  biliary 
secretions  together,  or  these  in  conjunction  with  the  intestinal 
juice,  have  a  bactericidal  action  is  not  yet  determined. 

In  the  large  intestine,  beginning  with  the  caecum,  the 
number  of  bacteria  increases  enormously  to  reach,  by  the 
time  the  rectum  is  reached,  the  gigantic  proportions  which 
have  been  discussed  above.  The  cause  of  the  prolific  develop- 
ment of  micro-organisms  in  the  large  intestine  is  by  no  means 
clear.  The  fact  that  the  intestinal  contents  assume  an 
alkaline   reaction   after    the    ileocecal   valve   is   passed   no 


THE  BACTERIA   OF   THE  ALIMENTARY   TRACT.    167 

doubt  plays  an  important  rule     Again,  the  time  which  the 

food  spends  in  this  part  of  (lie  intestinal  canal  is  far  greater 
than  that  in  any  <>f  the  preceding  portions,  so  that  the 
time  allowed  for  the  multiplication  of  the  bacteria  is  cor- 
respondingly greater.  We  must,  moreover,  remember  the 
antiperistaltic  movements  of  the  transverse  and  ascending 
colon  as  a  potent  factor  in  carrying  the  bacteria  from  the 
descending  arm  of  the  large  bowel  into  the  transverse  and 
ascending  portions  of  the  colon.  Bacteria  are  constantly 
entering  the  alimentary  tract  by  way  of  the  rectum.  Until, 
however,  we  are  better  acquainted  with  the  physiology  of 
the  development  and  growth  of  bacteria,  we  can  expect 
to  make  but  little  progress  in  this  as  well  as  in  other  branches 
of  bacteriology.  Systematic  studies  of  the  influence  of 
external  conditions  upon  bacteria,  such,  for  example,  as 
William  B.  Wherry1  has  recently  begun  on  cholera  and 
which  promise  so  much  in  the  advance  of  our  knowledge  of 
mycotic  diseases,  are  still  very  rare. 

The  question  naturally  suggests  itself  as  to  how  the  bac- 
teria get  from  the  mouth  into  the  large  bowel  if  the  stomach 
through  which  all  the  food  passes  has  such  well-marked 
bactericidal  action.  We  answer  this  question  at  present 
by  saying  that  the  bacteria  are  either  not  all  killed,  that 
they  pass  through  in  the  form  of  spores,  or  finally,  that 
they  are  not  affected  by  the  gastric  juice  because  they  are 
enclosed  in  particles  of  food.  But  even  the  practically 
empty  intestinal  tract  of  starvation  is  not  entirely  free 
from  bacteria,  from  which  the  conclusion  has  been  drawn 
that  the  intestine  has  a  flora  of  its  own.  Great  care  must, 
however,  be  exercised  in  accepting  this  view,  as  it  has  not 
yet  been  proved  that  the  various  bacteria  found  in  star- 
vation are  not  such  as  are  capable  of  living  on  the  secre- 
tions of  the  intestinal  mucosa  alone.  As  these  secretions 
are  different  in  different    portions  of  the  intestine  it   is  not 

'Wherry:   Journal  ol  Infectious  Diseases,  1905,  II,  p.  .'>U'.>. 


168  PHYSIOLOGY  OF  ALIMENTATION. 

strange  that  larger  numbers  of  micro-organisms  should  also 
live  in  some  portions  of  the  gut  than  in  others.  The  exist- 
ence of  a  greater  variety  of  bacteria  in  certain  portions  of 
the  alimentary  tract  would  also  increase  the  chances  for  a 
symbiotic  development  here.  At  any  rate  in  the  absence 
of  systematic  observations  on  the  effect  of  external  con- 
ditions upon  bacteria  we  must  be  exceedingly  careful  in 
accepting  any  explanation  of  their  distribution  throughout 
the  alimentary  tract  which  is  based  upon  purely  vitalistic 
conceptions. 

6.  Much  has  been  and  more  will  be  written  concerning 
the  influence  of  the  ordinary  bacterial  inhabitants  upon  the 
general  health  of  the  host.  The  majority  of  investigators 
seem  agreed  that  under  ordinary  circumstances  the  bac- 
teria of  the  alimentary  tract  (even  the  pathogenic  which 
are  found  here)  do  not  penetrate  the  intestinal  mucosa. 
Under  various  as  yet  entirely  unknown  conditions,  however, 
these  micro-organisms  may  pass  readily  through  the  wall 
of  the  gut.  This  is  very  generally  the  case  shortly  after 
death,  and  during  life  is  perhaps  the  cause  of  certain  local 
or  general  infections  which  start  from  the  intestinal  tract. 
Why  the  intestine  should  under  certain  circumstances  lose 
its  power  of  holding  back  these  micro-organisms  is  not  yet 
explained.  It  is  not  improbable,  however,  that  the  taking 
up  of  bacteria  by  the  cells  of  the  intestinal  wall  is  deter- 
mined at  least  in  part  by  the  same  circumstances  which 
determine  the  taking  up  of  bacteria  by  the  leucocytes, 
namely,  alterations  in  surface  tension.  It  would  not  be 
strange  to  find  that  all  those  conditions  which  determine 
the  entrance  of  bacteria  into  the  intestinal  mucosa  are  such 
as  alter  the  surface  tension  of  the  cells  composing  it. 

Even  if  under  ordinary  circumstances  bacteria  do  not  pass 
through  the  walls  of  the  alimentary  tract  the  same  cannot 
be  said  of  their  products.  Many  of  these  are  readily  diffusible 
and  so  are  absorbed.  These  products  of  bacterial  activity 
are  at  times  harmless,  at  other  times  intensely  poisonous. 


THE  BACTERIA    OF   THE   ALIMENTARY   TRACT.      1G9 

A  discussion  of  the  prod  mix  of  bacterial  activity  in  the 
alimentary  tract  is  therefore  next  in  order.  Without  enter- 
ing too  deeply  into  the  chemical  changes  which  the  indi- 
vidual varieties  of  bacteria  are  capable  of  producing  in  the 
intestinal  contents,  the  alimentary  flora  as  a  whole  may 
be  looked  upon  as  able  to  bring  about  the  following  well- 
established  decompositions.  The  amount  of  such  decom- 
positions is,  of  course,  again  dependent  upon  a  large  num- 
ber of  external  conditions,  of  which  we  need  mention  by 
way  of  illustration  only  the  character  and  amount  of  food 
consumed,  the  length  of  time  that  such  food  remains  in 
the  intestinal  tract,  the  reaction  of  the  intestinal  contents 
as  determined  by  physiological  or  pathological  variations 
in  the  secretions  poured  out  upon  the  food,  etc. 

The  bacteria  of  the  alimentary  tract  contain  in  their 
bodies  or  secrete,  first  of  all,  a  number  of  enzymes  which 
are  not  unlike  those  which  are  normally  poured  out  upon 
the  food  in  its  passage  from  mouth  to  anus.  We  need 
mention  here  only  amylase,  sucrase,  and  lactase,  which 
like  the  ferments  normally  poured  out  upon  the  food  con- 
vert starch  into  maltose,  cane-sugar  into  dextrose  and 
laevulose,  and  milk-sugar  into  dextrose  and  galactose.  Pro- 
teolytic enzymes  probably  identical  with  acid-  and  alkali- 
proteinase  (pepsin  and  trypsin)  are  also  found  in  the  ali- 
mentary bacteria.  By  virtue  of  these  they  not  only  split 
proteins  into  albumoses  and  peptones  but  even  into  the 
ultimate  digestion  products  (mono-  and  diamino-acids) 
with  which  we  have  already  become  acquainted  in  the  dis- 
cussion of  the  proteolytic  enzymes  found  in  the  alimentary 
secretions  proper.  Lipase  is  also  found  in  certain  of  the 
intestinal  bacteria,  so  that  the  presence  of  fatty  acid  in 
the  intestinal  contents  must  be  attributed  at  least  in  part 
to  the  activities  of  these  micro-organisms.  Atone  time  the 
presence  of  fatty  acids  in  the  stomach  in  cases  of  carci- 
noma and  other  diseases  which  may  be  associated  with  a 
decreased  amount  or  entire  lack  of  hydrochloric  acid  was 


170  PHYSIOLOGY  OF  ALIMENTATION. 

attributed  solely  to  the  activities  of  lipase-containing  bac- 
teria found  here.  Since  we  have  become  acquainted  with 
the  presence  of  lipase  in  the  normal  secretions  of  this  viscus, 
this  idea  must  be  modified,  and  the  two  sources  of  li- 
pase be  taken  into  consideration.  Mention  must  finally 
be  made  of  the  cytase  which  certain  of  the  intestinal  bac- 
teria contain.  This  ferment  has  the  power  of  acting  upon 
cellulose  and  converting  it  into  dextrin  and  glucose. 

From  what  has  been  said,  therefore,  it  can  readily  be 
seen  that  certain  of  the  bacteria  of  the  intestinal  tract  may 
even  be  of  service  to  the  animal  which  harbors  them,  for 
they  produce  changes  in  the  alimentary  contents  not  unlike 
those  brought  about  by  the  normal  secretions,  and  in  the 
last  example  cited  above,  they  may  even  render  an  other- 
wise useless  constituent  of  our  food  (the  cellulose  of  the 
vegetable  cells)  useful  to  the  animal  organism  by  convert- 
ing it  into  substances  which  can  be  taken  up  by  the  body. 
While  these  cytase-containing  bacteria  probably  play  only 
an  insignificant  role  in  the  digestive  processes  of  the  car- 
nivora,  the  herbivora  no  doubt  are  dependent  upon  these 
bacteria  in  no  mean  way,  for  even  if  the  amounts  of  dex- 
trin and  glucose  formed  in  the  hours  during  which  the  bac- 
teria are  active  are  not  very  large,  the  dissolution  of  the 
cellulose  walls  of  the  vegetable  cells  liberates  their  more 
readily  digestible  contents  and  so  puts  these  into  a  posi- 
tion to  be  absorbed. 

So  far  as  the  amount  of  the  just-described  forms  of  diges- 
tion of  which  the  various  bacteria  are  capable  is  concerned, 
it  is  no  doubt  correct  to  say  that  as  compared  with  the 
activities  of  the  normal  secretions  of  the  alimentary  tract 
this  is,  under  ordinary  circumstances,  comparatively  little. 

We  come  now  to  the  bacterial  decompositions  in  the  ali- 
mentary tract  which  are  apparently  of  no  service  to  the  host 
and  which  are  at  times  of  a  distinctly  injurious  character. 
It  is  these  that  have  excited  the  greatest  amount  of  medical 
discussion  and  have  led  to  the  volumes  of  literature  on  in- 


THE   HACTERJA  OF   THE   ALIMENTARY    TRACT      171 

testinal  putrefaction,  its  qualitative  and  quantitative  det<  r- 
mination,  its  physiological  and  pathological  importance,  and 
the  means  of  combating  it.  Of  the  nature  of  these  decompo- 
sitions we  know  as  yet  but.  little.  That  they  are  enzymatic 
in  character  is  proven  by  numerous  experiments  and  is  gen- 
erally conceded,  but  of  the  nature  of  the  individual  enzymes 
which  are  active  we  are  almost  entirely  ignorant,  as  also  of 
the  finer  chemistry  of  the  changes  which  occur  in  the  alimen- 
tary contents  in  their  transformation  into  the  substances 
which  we  recognize  as  the  products  of  bacterial  activity. 

When  the  alimentary  contents  are  analyzed  chemically  it 
is  found  that  a  fairly  distinct  division  can  be  made  between 
the  nature  of  the  substances  found  above,  and  those  dis- 
covered below  the  ileocsecal  valve.  The  bacterial  decom- 
position products  found  in  the  stomach  may  be  dismissed 
with  the  statement  that  under  normal  conditions  none 
are  found.  This  is  dependent  upon  a  number  of  facts: 
first  of  all  the  high  acidity  of  the  gastric  juice  which  lies 
far  above  the  limits  inside  of  which  most  fermentative 
changes  can  take  place,  and  secondly,  the  short  time  (at 
most  a  few  hours)  that  the  food  remains  in  this  viscus.  What- 
ever bacterial  decompositions  are  possible  in  the  stomach 
can,  therefore,  never  reach  a  high  grade  in  the  limited  time 
allowed  for  such  changes  under  normal  circumstances.  The 
physiological  importance  of  these  two  circumstances  mani- 
fests itself  most  clearly  when  through  experiment  or  disease 
they  are  missing.  Every  day  clinical  observation  suffices  to 
show  how  the  stomach  contents  of  a  patient  whose  gastric 
juice  contains  too  little  acid,  or  whose  stomach  does  not 
empty  itself  except  after  long  intervals,  are  teeming  with 
bacteria  and  the  products  of  I  heir  enzymatic  activities. 
These  products  differ  and  fall  into  the  group  of  those  derived 
from  the  fats,  carbohydrates,  or  proteins  of  the  ingested  food 
according  to  the  conditions  found  in  the  stomach  as  deter- 
mined by  the  changes  in  the  viscus  itself,  the  food,  and  the 
character  of  the  bacteri;    i  n  sent. 


172  PHYSIOLOGY  OF  ALIMENTATION. 

Our  knowledge  of  the  bacterial  products  present  in  the 
small  intestine  of  the  human  being  has  been  derived  from 
analyses  of  intestinal  contents  obtained  from  patients  suf- 
fering from  intestinal  fistulse.  The  observers  who  have 
worked  in  this  field  all  agree  that  the  contents  of  the  small 
intestine  are  acid  in  reaction,  determined,  however,  not  by 
free  hydrochloric  acid,  but  by  fatty  acids  resulting  in  the 
main  from  the  activity  of  the  lipase  produced  by  the  pancreas 
and  the  intestinal  wall  upon  the  fats  of  the  food,  but  also  in 
part  due  to  the  action  of  lipase-containing  bacteria.  No  in- 
considerable amount  of  acid  seems  to  be  derived  from  the 
carbohydrates  through  the  action  upon  them  of  the  bacteria 
found  in  the  small  intestine.  Among  the  acids  formed  in 
this  way  in  small  amounts  under  normal  conditions,  and  in 
often  enormous  amounts  in  pathological  states  may  be  men- 
tioned acetic,  different  kinds  of  lactic,  succinic,  butyric,  and 
formic  acids.  The  excessive  formation  of  these  acids  is  at 
once  brought  about  when  from  any  cause — such  as  insuf- 
ficiency of  the  secretions  of  the  alimentary  tract,  or  insuf- 
ficiency of  the  proper  ferments  in  these  secretions,  or  enjoyment 
of  excessive  amounts  of  carbohydrates — these  are  not  digested 
and  absorbed  in  the  proper  way  and  so  become  the  prey  of 
the  bacteria  always  present  here.  The  formation  of  small 
amounts  of  these  organic  acids  need  not  be  followed  by  se- 
rious consequences.  Small  amounts  may  be  absorbed,  oxi- 
dized in  the  tissues,  and  no  evil  consequences  result.  Others 
undergo  further  change  in  the  alimentary  tract  and  are  con- 
verted into  water,  carbon  dioxide,  marsh-gas,  and  hydrogen. 
The  organic  acids  produced  bring  about,  even  in  small  amounts, 
an  increased  peristalsis  and  an  increased  secretion  of  water 
into  the  intestine,  so  that  if  the  condition  is  at  all  marked, 
frequent  liquid  stools,  acid  in  reaction  and  ill-smelling,  result. 
The  presence  -of  gases  in  the  intestines  also  induces  peristalsis. 
It  is  clear  that  a  slight  alimentary  fermentation  need  not 
be  an  evil  thing.  Unquestionably  the  beneficent  effects  of 
the  addition  of  vegetables  to  an  ordinary  mixed  diet  in  bring- 


THE  BACTERIA  OP   THE  ALIMENTARY   TRACT.     173 

ing  about  a  more  regular  discharge  of  the  faeces  is  due  quite 
as  much  to  the  fact  that  the  celluloses,  starches,  and  sugars 
contained  in  the  vegetables  are  not  readily  attacked  (because 
of  their  structure)  by  the  alimentary  enzymes  and  so  furnish 
a  culture  medium  for  the  intestinal  flora  with  the  product  inn 
of  the  above-mentioned  acids  and  gases  as  to  any  "mechani- 
cal "  stimulation  which  a  coarse  food  is  supposed  to  exert. 

It  will  not  seem  surprising  that  acute  alimentary  fer- 
mentations (with  diarrhoea  and  the  general  symptoms  of 
intoxication)  are  much  more  common  after  the  enjoyment 
of  excessive  amounts  of  disaccharides  (candy,  milk-sugar) 
than  after  the  use  of  equally  large  amounts  of  starch.  Not 
only  does  the  absorption  of  the  sugar  formed  from  starch 
ordinarily  keep  pace  with  its  production,  but  the  starches 
themselves  do  not  furnish  as  favorable  a  culture  medium 
for  the  bacteria  as  do  cane-sugar  and  milk-sugar  for  example. 
These  two  are  not  only  absorbed  comparatively  slowly,  but 
they  are  readily  attacked  by  bacteria. 

Products  of  protein  decomposition  such  as  are  generally 
looked  upon  as  characteristic  of  the  fermentative  activities 
of  bacteria  are  found  in  the  small  intestine  either  not  at  all 
or  only  in  small  quantities. 

With  the  passage  of  the  alimentary  contents  through  the 
ileocecal  valve  a  complete  change  occurs  in  the  type  of 
bacterial  decomposition  found.  Instead  of  the  products 
of  the  decomposition  of  carbohydrates  we  find  now  the 
products  of  protein  decomposition.  This  change  is  deter- 
mined by  a  number  of  conditions;  which  is  primary  and 
which  is  secondary  cannot  be  easily  discovered.  As  the 
alimentary  contents  pass  along  the  small  intestine  they 
become  progressively  poorer  in  carbohydrates,  so  lh.it  by 
the  time  the  ileocecal  valve  is  reached  little  or  none  arc 
left  to  be  absorbed.  The  reaction  of  the  alimentary  con- 
tents also  changes.  While  above  the  ileoca?cal  valve  the 
intestinal  contents  are  acid,  they  are  alkaline  below  it. 
The  character  of  the  bacterial  (i<  ra  as  already  outlined  above 


174  PHYSIOLOGY  OF  ALIMENTATION. 

also  changes  as  we  pass  through  the  ileocaecal  valve,  but 
here  again  it  is  difficult  to  decide  whether  the  intestinal 
contents  determine  the  character  of  the  flora  or  vice  versa. 
The  fact  remains,  however,  that  while  in  the  small  intestine 
we  deal  chiefly  with  the  products  of  carbohydrate  decom- 
position we  have  to  do  in  the  large  bowel  chiefly  with  the 
products  of  protein  decomposition.  By  virtue  of  the  or- 
dinary proteolytic  enzymes  contained  in  the  bacteria  the 
undigested  proteins  suffer  a  successive  cleavage  into  pro- 
teoses, peptones,  and  finally  amino-acids.  The  decompo- 
sition does  not  cease  here  but  continues  in  two  directions. 
First  of  all  the  amino  group  may  be  split  off  so  that  simple 
organic  acids  are  left  behind.  Acetic  acid  is  in  consequence 
formed  from  glycocoll,  propionic  acid  from  alanin  and 
valerianic  acid  from  amino-valerianic  acid.  Succinic  acid, 
phenylpropionic  acid,  oxyphenylpropionic  acid,  and  skatol- 
acetic  acid  may  also  be  found.  Secondly,  carbon  dioxide 
may  be  split  off  from  the  amino-acids  with  the  formation  of 
such  substances  as  cadaverin  and  putrescin.  Through  fur- 
ther oxidation  we  obtain  phenol,  indol,  and  skatol.1  These 
in  combination  with  sulphuric  acid  are  excreted  in  the  urine. 
Their  quantitative  estimation  in  the  urine  has  in  conse- 
quence been  utilized  as  a  test  of  the  amount  of  putrefac- 
tion going  on   in  the  alimentary  tract. 

To  the  volatile  fatty  acids  and  aromatic  compounds  and  to 
certain  of  the  gases  formed  in  the  action  of  the  bacteria  upon 
the  alimentary  contents  is  due  the  odor  of  the  faeces  and 
flatus. 

From  what  has  been  said  in  the  preceding  paragraphs  it 
might  be  concluded  that  the  bacteria  of  the  alimentary  canal 
are  either  always  harmful  or  at  the  best  of  no  use  to  the 
host.  This  is,  however,  not  the  case.  It  has  been  shown 
through  the  experiments  of  Nuttall  and  Thierfeldbr2  that 

1  Abderhalden •  Physiol.  Chemie,  Berlin,  1906,  p.  1S4. 

2  Nuttall  andTHiERFELDER:  Zeitschr.  f.  Physiol.  Chemie,  1895,  XXI 
p.  109;  ibid.,  1896,  XXII,  p.  62. 


THE  BACTERIA   OF  THE  ALIMENTARY   TRACT.     175 

they  may  even  serve  a  good  purpose,  for  young  guinea- 
pigs  removed  from  the  uterus  by  Cacsarean  section  and 
kept  in  sterile  vessels,  given  sterile  air  to  breathe  and  sterile 
food  to  eat  do  not  thrive  as  do  animals  from  the  same 
litter,  born  under  the  same  circumstances  but  raised  in 
ordinary  air  and  on  non-sterilized  food.  It  was  found  that 
the  latter  were  uniformly  better  nourished,  heavier,  and 
lived  longer  than  the  former.  Schottelius1  has  made  simi- 
lar experiments  on  chicks  and  has  found  that  when  kept 
under  absolutely  sterile  conditions  these  fowls  in  twelve 
days  increase  only  25  percent  in  weight  instead  of  140  per- 
cent, as  do  the  control  animals. 

1  Cited    from  Kohlbrugge:    Centralbl.  f.  Bakt.,  1901,  XXX,  lte 
Abth.,  p.  26. 


CHAPTER  X. 
THE  REGULATION  OF  SALIVARY  SECRETION. 

i.  Salivary  Fistulae. — The  salivary  glands  have  since  the 
earliest  days  of  experimental  physiology  served  as  objects 
of  investigation,  partly  through  the  fact  that  changes  in 
the  character  of  their  secretions  from  time  to  time  are  readily 
apparent  and  partly  because  their  superficial  situation  ren- 
ders them  easily  accessible  to  study. 

In  order  to  determine  the  quantitative  or  qualitative 
changes  in  the  saliva  as  it  is  poured  out  by  the  three  pairs 
of  parotid,  submaxillary,  and  sublingual  glands  it  is  necessary 
to  collect  the  saliva  as  it  issues  from  the  ducts.  It  is  pos- 
sible to  accomplish  this  in  man  and  various  animals  by 
inserting  fine  catheters  into  the  ducts  of  these  glands  and 
allowing  the  saliva  to  drip  into  small  glass  tubes.  Some- 
times nature  creates  salivary  fistulae  which  open  externally, 
as  when  salivary  calculi  ulcerate  through  the  cheek  or  injuries 
of  various  kinds  to  a  salivary  gland  or  its  excretory  duct 
cause  the  saliva  to  flow  out  upon  the  skin.  The  study  of 
such  cases  has  yielded  many  valuable  physiological  data. 

The  older  investigators,  in  their  animal  experiments,  used 
to  lay  bare  the  different  salivary  glands,  catheterize  the  ducts 
and  collect  the  saliva  which  poured  out  of  them.  Today,  how- 
ever, when  we  have  learned  how  much  narcotics  and  various 
operative  procedures  interfere  with  the  normal  function  of  an 
organ  we  try  to  employ  experimental  procedures  which  do 
away  with  such  disturbing  influences.  In  a  large  number  of 
experiments  it  is  possible  therefore  to  work  on  animals  in 

176 


THE  REGULATION  OF  SALIVARY   SECRETION.      177 

which  through  previous  operation  the  salivary  ducts  have 
been  turned  outward  in  such  a  way  that  they  pour  their 
secretions  upon  the  skin  where  they  may  be  collected  and 
studied.  Not  only  do  such  measures  bring  with  them  a 
great  saving  of  animals,  but  they  constitute  the  only  means 
by  which  we  can  obtain  a  true  conception  of  the  normal 
activity  of  the  gland.  How  revolutionary  are  the  results 
obtained  by  such  experimental  means  which  to  all  intents 
and  purposes  leave  the  laboratory  animals  uninjured,  not 
only  in  the  case  of  the  salivary  glands  but  all  the  digestive 
glands,  will  be  readily  apparent  from  the  pages  that  follow. 
We  will  describe  first  of  all  Glinnski  and  Pawlow's1 
method  of  making  a  permanent  salivary  fistula.  A  dog  is  ordi- 
narily used.  If  the  parotid  saliva  is  to  be  collected  a  small 
sound  is  intioduced  into  Stenson's  duct  and  under  chloroform 
anaesthesia  a  circular  incision  is  made  through  the  mucous 
membrane  around  the  orifice  of  the  duct.  The  duct  is  care- 
fully dissected  free  from  its  surrounding  tissues  and  a  hole  is 
punched  through  the  cheek  by  means  of  a  sharp  knife.  The 
duct  is  drawn  through  this  hole  and  the  collar  of  mucous 
membrane  is  sewed  into  the  edges  of  the  hole.  After  healing 
is  complete  the  parotid  discharges  its  secretion  upon  the 
cheek.  For  a  study  of  the  secretions  of  the  submaxillary  and 
sublingual  glands  a  similar  procedure  is  followed,  but  since 
it  is  not  an  easy  matter  to  separate  the  ducts  of  'Wharton 
and  of  Bartholin  the  two  are  usually  together  sewed  into  the 
edges  of  the  external  wound.  After  everything  is  healed  the 
secretions  from  the  two  glands  can  be  separated  by  a  sec- 
ondary operation  in  which  the  ducts  are  ligatured  and  opened 
on  the  side  nearest  the  gland.  In  order  to  collect  the  saliva 
which  flows  from  the  glands  small  flanged  glass  funnels  are 
pasted  over  the  openings  by  means  of  a  laboratory  paste,  and 
from  the  points  of  these  funnels  small  graduated  tubes  are 
suspended.     A  dog  which  has  had  one  or  two  glands  operated 

'Glinnski  and  Pawlow:  Ergebnisse  Ucr  Physiologie,  1902,  1,  lte 
Abth.,  p.  252. 


178  PHYSIOLOGY  OF  ALIMENTATION. 

upon  in  the  way  indicated  suffers  absolutely  no  inconve- 
nience, if  only  care  be  taken  to  have  the  food  fed  the  animal, 
when  not  being  used  for  experimental  purposes,  sufficiently 
moist. 

2.  The  Relation  of  the  Nerves  to  the  Salivary  Secretions. 
— Each  of  the  three  sets  of  salivary  glands  is  supplied  by  two 
sets  of  nerves,  the  one  being  of  cranial  origin,  the  other  of 
sympathetic.  The  submaxillary  and  sublingual  glands  are 
supplied  by  a  branch  of  the  facial  nerve — the  chorda  tympani. 
The  parotid  is  supplied  by  the  auriculo -temporal  branch  of  the 
trifacial  nerve.  The  sympathetic  fibres  are  derived  in  the 
main  from  the  second,  third,  and  fourth  thoracic  nerves, 
which,  after  passing  into  the  sympathetic  chain,  ascend  to 
the  superior  cervical  ganglion,  from  which  nerve  fibres,  chiefly 
of  the  non-medullated  variety,  are  given  off  that,  after  follow- 
ing the  external  carotid  artery,  are  finally  distributed  to  the 
various  salivary  glands.  Let  us  see  now  what  the  effect  of 
division  and  electrical  stimulation  of  these  various  nerves  is. 
In  spite  of  the  many  contradictory  statements  found  in  the 
original  papers  of  different  investigators,  these  all  seem  to 
agree  on  the  following  points. 

If  a  glass  catheter  is  introduced  into  the  duct  of  a  salivary 
gland,  no  or  only  very  little  secretion  flows  from  it  under 
ordinary  circumstances.  If  now  the  cranial  nerve  supplying 
the  gland  is  laid  bare  (for  example,  the  chorda  tympani  nerve 
to  the  submaxillary  gland  of  a  dog)  and  divided  with  a  snip 
of  the  scissors,  no  change  occurs.  Let,  however,  the  peripheral 
end  of  the  divided  nerve  be  stimulated  electrically,  mechani- 
cally, or  chemically,  and  the  saliva  is  seen  to  move  along  the 
catheter  with  increased  rapidity.  Soon  a  drop  falls  from  its 
end,  and  this  is  followed  by  another  and  another  in  rapid 
succession.  By  far  the  most  effective  form  of  stimulation  is 
that  with  repeated  induction  shocks.  A  very  weak  current 
will  bring  about  such  an  increased  flow  of  saliva,  but  within 
certain  limits  the  stronger  the  current  the  greater  the  flow 
of  saliva.     Since  the  stronger  currents  injure  the  nerve,  the 


THE  REGULATION  OF  SALIVARY  SECRETION.     179 

length  of  time  during  which  the  ll<>\v  of  saliva  can  be  kept 
up  under  these  circumstances  is  appreciably  less  than  when  a 
weaker  current  is  used.  In  a  properly  arranged  experiment 
with  a  moderate  currenl  a  flow  of  saliva  may  be  maintained 
an  hour  or  more. 

The  submaxillary  of  the  dog  may  secrete  in  five  minutes 
an  amount  of  saliva  equal  to  its  own  weight,  and  by  alter- 
nately .stimulating  and  resting  the  gland  250  c.c.  may  be 
obtained  in  1()  to  12  hours.  Toward  the  end  of  this  time 
the  rate  of  flow  is  less  than  at  the  beginning  of  the  experi- 
ment.1 

Some  difference  exists  in  the  amount  and  in  the  character 
of  the  saliva  as  obtained  from  the  different  glands  in  different 
animals.  In  the  dog  stimulation  of  the  auriculo-temporal 
nerve  supplying  the  parotid  by  methods  similar  to  those  just 
described  yields  from  one-half  to  two-thirds  the  amount  of 
saliva  obtained  from  the  submaxillary  gland.  This  agrees 
with  Claude  Bernard's  finding  that  when  saliva  is  obtained 
refiexly  from  the  dog  the  submaxillary  gland  furnishes  twice 
as  much  as  the  parotid  and  ten  times  as  much  as  the  sub- 
lingual gland. 

While  the  composition  of  the  saliva  as  obtained  from  the 
different  glands  when  their  cranial  nerves  are  stimulated  is 
not  the  same  (the  submaxillary  saliva,  for  example,  always 
contains  more  organic  matter  than  either  the  sublingual  or 
parotid,  and  the  sublingual  more  salts  than  either  of  the  other 
two),  still  it  is  in  all  cases  clear,  thin,  and  watery,  and  contains 
only  from  1  to  2  percent  of  solid  matter. 

Exposure,  section,  and  stimulation  of  the  sympathetic 
fibres  going  to  one  of  the  salivary  glands  is  followed  by  quite 
a  different  effect.  In  this  case  also  a  flow  of  saliva  is  ob- 
tained, only  much  less  than  when  the  corresponding  cranial 
nerve  is  stimulated,  and  the;  saliva  has  entirely  different 
characteristics.     While  histological  study  may  show  that  a 

1  Langley:  Schaefcr's  Text-book  of  Physiology,  1900,  Vol.  I,  p.  493. 


180  PHYSIOLOGY  OF  ALIMENTATION. 

secretion  of  saliva  has  occurred  in  a  gland  shortly  after  stimu- 
lation, as  evidenced  by  the  presence  of  saliva  in  the  smaller 
ducts  of  the  gland,  external  evidence,  that  is  a  movement  of 
saliva  in  the  glass  catheter  inserted  into  the  duct  of  Wharton, 
Stenson,  or  Bartholin,  is  not  so  readily  obtained.  Such  a 
movement  is  discoverable  only  after  stimulation  has  been 
continued  for  some  time  and  not  witkin  a  few  seconds,  as 
when  the  cranial  nerves  are  stimulated.  Langley  has  calcu- 
lated that  at  the  best  only  1/30  to  1/60  of  the  quantity  of 
saliva  which  would  be  obtained  from  the  submaxillary  gland 
were  the  chorda  tympani  stimulated  is  obtained  when  the 
sympathetic  fibres  of  the  same  gland  are  stimulated. 

In  contrast  to  the  clear  watery  saliva  obtained  through 
stimulation  of  the  cranial  fibres,  that  obtained  when  the 
sympathetic  fibres  of  one  of  the  salivary  glands  is  stimu- 
lated is  turbid,  thick,  and  ropy.  While  in  such  sympa- 
thetic saliva  great  variations  in  chemical  composition  are 
also  found  in  different  animals,  it  can  be  said  in  general 
that  it  is  much  richer  in  organic  and  inorganic  material 
than  is  cranial  saliva,  containing  as  it  does  on  an  average 
of  from  3  to  4  percent  solids. 

Various  attempts  have  been  made  to  explain  these  differ- 
ences in  the  chemical  composition  of  the  various  salivas 
and  in  the  quantities  secreted.  The  nerves  have  been 
charged  with  a  multiplicity  of  functions,  but  none  of  these 
explanations  can  as  yet  be  regarded  as  satisfactory. 

Stimulation  of  the  nerves  supplying  a  salivary  gland  is 
accompanied  by  a  series  of  accessory  phenomena  which 
deserve  notice.  When  induction  shocks  are  applied  to  the 
chorda  tympani  nerve,  for  example,  not  only  does  the  rate 
of  salivary  secretion  increase,  but  the  gland  swells,  becomes 
redder  in  color,  and  the  efferent  veins  pulsate  with  arterial 
blood.  The  chorda  tympani,  in  other  words,  carries  vaso- 
motor nerves  to  the  gland.  It  was  once  thought  that  the 
increased  secretion  of  saliva  was  due  to  this  increased  flow 
of  blood  through  the  gland,  but  this  can  no  longer  be  held. 


THE  REGULATION  OF  SALIVARY  SECRETION.      181 

It  has  been  found  that  for  a  short  time  at  least,  a  secretion 
of  saliva  can  be  obtained  even  from  the  head  of  a  decapi- 
tated animal,  in  other  words,  in  the  entire  absence  of  a 
circulation.  That  such  a  secretion  continues  no  longer 
than  it  docs  is  not  strange,  for  in  the  end  all  the  constituents 
of  a  secretion,  not  the  least  important  of  which  is  the  water 
itself,  must  be  obtained  from  the  blood.  The  increased  blood- 
pressure,  which  has  so  often  and  so  long  been  considered  the 
determining  factor  in  increasing  the  amount  of  the  salivary  as 
well  as  the  amount  of  other  secretions,  can  by  itself  be  of 
little  moment,  as  is  shown  by  Ludwig's  classical  observa- 
tion. When  the  outflow  of  saliva  from  the  salivary  duct 
is  prevented,  the  pressure  in  this  duct  may,  when  the  chorda 
tympani  is  stimulated,  rise  far  above  that  found  in  even 
the  larger  arteries,  such  as  the  carotid.  Finally,  it  is  pos- 
sible to  bring  about  a  vascular  dilation  in  a  salivary  gland  and 
yet  get  no  secretion.  This  happens  when,  after  a  dose  of 
atropin,  the  chorda  tympani  or  the  auriculo-temporal  nerve 
is  stimulated.  The  converse  of  this  experiment  can  be 
performed  with  pilocarpin.  When  this  alkaloid  is  injected, 
a  free  flow  of  saliva  is  brought  about,  even  when  no  change 
has  occurred  in  the  calibre  of  the  blood-vessels. 

Besides  the  change  which  occurs  in  the  calibre  of  the 
blood-vessels  supplying  a  salivary  gland,  there  is  also  a 
change  in  temperature.  The  active  gland  becomes  warmer. 
The  amount  of  thermal  change  is  not  determined  simply 
by  the  arterial  blood  coursing  through  the  gland.  As 
Ludwig  and  Spiess  have  shown,  when  one  thermometer  is 
inserted  into  the  secretory  duct  of  the  submaxillary  of  a 
dog,  a  second  into  the  efferent  vein,  and  a  third  into  the 
carotid  artery,  then,  when  the  gland  is  excited  to  secretion 
by  stimulation  of  the  chorda  tympani,  the  thermometers 
in  the  duct  and  in  the  vein  register  a  higher  temperature 
than  the  thermometer  in  the  carotid.  This  observation  is 
of  fundamental  importance,  as  it  gives  us  some  clue  to  the 
character    of    the    changes    which    occur    in    salivary    and 


182  PHYSIOLOGY  OF  ALIMENTATION. 

other  glands  during  activity.  Such  a  rise  in  temperature 
means  that  exothermic  reactions  are  taking  place  within 
the  gland.  These  exothermic  reactions  may  be  chemical, 
and  we  find  support  for  this  idea  in  the  well-known  fact 
that  an  active  salivary  gland  consumes  more  oxygen  and 
gives  off  more  carbon  dioxide  than  a  resting  one.  We  are 
dealing  therefore  with  oxidations  in  the  gland.  But  from 
Mathews'  experiments  we  know  that  lack  of  oxygen  increases, 
at  least  within  certain  limits,  the  secretions  of  the  salivary 
glands.  Under  such  circumstances  the  heat  would  have  to 
come  from  intramolecular  oxidations,  in  other  words,  from 
the  analysis  of  complex  compounds  into  simpler  ones.  We 
meet  with  less  difficulty  if  we  seek  the  source  of  at  least 
part  of  the  heat  that  is  set  free  in  certain  physical  changes. 
Of  primary  importance  in  this  connection  is  the  well-known 
fact,  which  Pauli  has  studied  with  particular  care,  that  col- 
loids in  absorbing  water  set  heat  free.  The  swelling  of 
mucin  and  other  colloids  found  in  saliva  might  well  there- 
fore be  considered  as  sources  of  heat.  Mathews'  observa- 
tions would  also  find  an  explanation,  for  an  accumulation 
of  carbon  dioxide  or  the  various  poisonous  substances  formed 
in  living  tissues  in  the  absence  of  oxygen  all  increase  the 
affinity  of  tissues  for  water. 

We  have  yet  to  mention  the  paralytic  secretion  of  Claude 
Bernard.  When  both  the  cranial  and  sympathetic  nerve 
fibres  passing  to  a  gland  are  cut,  all  secretion  ceases.  After  a 
few  hours  the  secretion  begins  once  more  and  continues  for 
days.  Then  the  secretion  falls  off  again  and  finally  ceases. 
Whether  the  secretion  is  due  to  degeneration  (and  supposedly 
stimulation)  of  the  nerve  and  ceases  when  this  is  complete, 
as  is  generally  believed,  or  whether  the  atrophy  which  the 
gland  gradually  undergoes  is  the  real  cause  of  the  cessation, 
is  not  yet  settled. 

3.  The  Reflex  Secretion  of  Saliva. — Having  determined 
the  nervous  paths  over  which  impulses  may  reach  the  salivary 
glands  and  excite  them  to  activity,  we  have  to  discover  the 


THE  REGULATION  01    SAL/1    IRY   SECRETION.      183 

means  by  which  such  impulses  are  made  to  traverse  these 
nerves.  Jt  has  been  a  long-recognized  fact  that  the  flow  of 
saliva,  which,  under  ordinary  circumstances  is  not  more  than 

sufficient  to  keep  the  mouth  comfortably  moist,  is  enormously 
increased  as  soon  as  sweet,  bitter,  or  dry  substances  are  taken 
into  the  mouth,  a  piece  of  rubber  is  chewed,  or  the  mind 
dwells  for  a  few  seconds  upon  the  enjoyment  of  some  food. 
That  so  many  and  such  diverse  stimuli  are  capable  of  bring- 
ing about  an  increased  flow  of  saliva  has  naturally  led  to  the 
conclusion  that  any  stimulus  is  effective  in  this  direction. 
This  is,  however,  not  the  case,  as  can  be  shown  very  well  on 
dogs  having  permanent  salivary  fistulae,  operated  on  as  de- 
scribed in  the  first  section  of  this  chapter. 

A  mechanical  stimulus  is  either  unable  to  bring  about  a 
flow  of  saliva,  or  at  the  best  the  secretion  of  only  a  few  drops. 

If  some  pebbles  are  thrown  to  a  dog  from  some  distance, 
so  that  the  mechanical  stimulus  is  fairly  strong,  he  catches 
them,  may  move  them  about  in  his  mouth,  even  swallow  a 
few  of  them,  and  yet  no  saliva  flows.  Or  if  ice-water  is  poured 
into  the  mouth,  or  some  snow  is  thrown  in,  no  saliva  flows. 
But  let  some  sand  be  thrown  into  the  mouth  and  the  saliva 
flows  in  quantities.  The  same  is  true  of  all  substances  which 
the  dog  rejects — acids,  alkalies,  salts,  or  bitters.  There 
seems,  therefore,  to  be  a  purposeful  element  in  the  secretion 
of  the  saliva,  for  it  does  not  flow  when  substances  which  do 
not  need  it,  such  as  water,  are  taken  into  the  mouth,  but  it 
does  as  soon  as  substances  which  are  to  be  rejected,  or  which 
need  to  be  neutralized,  diluted,  or  washed  out  of  the  mouth 
are  taken.  The  degree  of  dryness  of  the  food  determines 
the  amount  of  saliva  poured  out  upon  it — the  drier  the  food 
the  larger  the  amount  of  saliva  that  is  secreted.  This  pur- 
poseful element  seems  still  more  striking  when  it  is  found, 
as  experiment  shows,  that  a  thin  and  watery  saliva  is  always 
poured  out  upon  substances  which  are  to  be  rejected,  while 
upon  edible  substances  a  saliva  rich  in  mucin,  one,  therefore, 
which   lubricates   the   bolus  to  be  swallowed  and  facilitates 


184  PHYSIOLOGY  OF  ALIMENTATION. 

its  descent  through  the  oesophagus,  is  s<  ireted.  Still, 
great  care  must  be  exercised  in  looking  upon  every  re- 
action of  an  organism,  or  one  of  its  organs  as  eminently  pur- 
poseful (as  does  Pawlow1),  and  therefore  for  the  ultimate 
good  of  the  organism.  We  are  familiar  with  too  many  illus- 
trations of  the  fact  that  living  matter  may  possess  character- 
istics that  are  eminently  dangerous  to  its  life  and  well-being. 

Of  much  interest  is  the  connection  between  the  physi- 
ology and  what  may  be  called  the  psychology  of  the  salivary 
glands.  We  see  in  the  facts  about  to  be  discussed  a  strik- 
ing illustration  of  how  the  organic  functions  of  an  organ  may 
be  markedly  influenced  through  the  state  of  the  mind — an 
illustration  not  without  interest  to  the  clinicist.  The  same 
series  of  reactions  can  be  obtained  as  have  been  described 
above,  when  the  animal's  attention  is  simply  directed  to  the 
substances  in  question.  When  the  experimenter  simply  pre- 
tends to  throw  pebbles  or  snow  into  the  mouth  of  the  dog  no 
secretion  follows,  but  the  saliva  flows  copiously  if  sand  takes 
the  place  of  the  pebbles.  If  various  kinds  of  food  are  offered 
the  animal,  saliva  flows  or  not,  just  as  though  the  animal  had 
been  really  feed  them.  Moreover,  the  same  qualitative  varia- 
tions are  noted  in  the  saliva.  If  the  proffered  food  is  dry, 
much  watery  saliva  is  secreted,  while  a  slimy  saliva  less  in 
amount  is  poured  out  when  meat  is  offered. 

Brief  mention  must  now  be  made  of  the  paths  over  which 
impulses  travel  to  the  cranial  and  sympathetic  nerve  fibres 
which  supply  the  salivary  glands  and  influence  their  secre- 
tions. Both  these  sets  of  nerve  fibres  originate  from  the 
medulla  or  in  the  pons  and  spinal  cord  just  above  and  below 
this.  Claude  Bernard's  experiments  are  therefore  of  great 
interest,  which  show  that  injury  to  certain  portions  of  the 
medulla  causes  a  copious  flow  of  saliva.  Whatever  means 
be  employed  in  bringing  about  a  reflex  secretion  of  saliva, 
this   can  only  be   possible   through  impulses   passing  from 

'  See  Pawlow:  Work  of  the  Digestive  Glands.  Translated  by 
Thompson,  London,  1902,  pp.  151  and  152, 


THE  REGULATION  OF  SALIVARY  SECRETION.     185 

the  periphery  into  the  medulla, and  from  here  over  the  various 
nerves  to  the  salivary  glands.  Most  of  the  peripheral  stimuli 
which  call  forth  a  secretion  of  saliva  originate,  no  doubt, 
in  the  mouth.  When  food  is  taken  into  the  mouth,  it  acts 
upon  the  gustatory  nerve  and  the  glosso-pharyngeal,  and 
these  constitute  the  afferent  nerves  over  which  impulses 
reach  the  medulla.  But  many  other  afferent  nerves  exist 
which  can  bring  about  a  flow  of  saliva.  When  the  sight  of 
food  is  effective  in  this  direction,  the  impulses  travel  over 
the  optic  nerves  into  the  large  nuclei  at  the  base  of  the  brain, 
from  where,  apparently,  connection  is  made  with  the  medulla. 
When  smell  causes  a  reflex  secretion  of  saliva,  the  impulses 
must  reach  the  uncinate  gyrus  and  from  here  connect  with 
the  medulla.  Of  interest  is  the  great  flow  of  saliva  which 
accompanies  feelings  of  nausea.  In  certain  cases  we  deal 
apparently  with  a  stimulation  of  the  endings  of  the  vagus 
nerve  over  which  impulses  travel  into  the  medulla.  In 
others  the  agencies  effective  in  bringing  about  the  feeling 
of  nausea  (as  in  sea-sickness)  may  influence  the  medulla, 
in  part  at  least,  directly.  The  medulla  from  which  the  nerve 
fibres  supplying  the  salivary  glands  arise  is  intimately  con- 
nected with  the  cerebral  cortex.  For  this  reason  the  mere 
thought  of  pleasant  or  unpleasant  things  may  cause  a  flow 
of  saliva.  As  experimental  evidence  of  such  a  connection  we 
have  the  well-known  fact  that  stimulation  of  certain  portions 
of  the  cerebral  cortex  causes  a  free  flow  of  saliva. 

We  have  thus  far  limited  ourselves  to  a  discussion  of  the 
three  great  pairs  of  salivary  glands.  The  many  small  glands 
scattered  throughout  the  mucous  membrane  lining  the  oral 
cavity  give  off  no  inconsiderable  secretion  as  their  contri- 
bution to  the  ordinary  mixed  saliva  found  in  the  mouth 
and  poured  out  upon  the  food.  We  have  little  accurate 
knowledge,  however,  regarding  the  means  by  which  the 
secretion  from  these  small  glands  is  ordinarily  controlled. 
Apparently  they  arc  more  or  less  independent  of  the  ('(Mi- 
tral  nervous  system,   for   when   the  ducts   of    all    the    large 


186  PHYSIOLOGY  OF  ALIMENTATION. 

salivary  glands  are  turned  outward,  sufficient  saliva  is  still 
secreted  to  keep  the  mouth  moist,  and  according  to  Colin 
this  may  amount,  even  while  no  food  is  being  chewed,  to 
from  100  to  150  c.c.  an  hour  in  the  horse. 

4.  On  the  Nature  of  Salivary  Secretion. — The  impression 
might  readily  be  obtained  from  the  preceding  paragraphs 
that  the  secretion  of  saliva  is  primarily  a  nervous  act.  This 
is,  of  course,  not  the  case,  and  in  the  last  analysis  the  secre- 
tion of  saliva  must  be  regarded  as  a  function  of  the  cells 
themselves  constituting  the  salivary  glands,  only  their 
activity  is  markedly  influenced  through  impulses  which 
pass  to  them  over  the  nerves  connected  with  them.  We 
have  already  mentioned  the  fact  that  the  salivary  glands 
will  secrete  (paralytic  secretion)  when  all  the  nerves  sup- 
plying them  have  been  cut.  It  is  much  more  reasonable 
to  suppose  that  this  secretion  is  an  expression  of  activity 
on  the  part  of  the  glands  themselves  than  one  induced 
through  stimuli  passing  into  them  from  the  cut  nerves. 
In  a  similar  way  modern  experiments  with  atropin,  pilo- 
carpi, and  other  poisons  seem  to  indicate  that  their  action 
is  at  least  not  limited  to  their  effect  upon  the  nerves,  if  per- 
haps they  do  not  act  solely  upon  the  secreting  epithelium  itself. 

We  know  as  yet  nothing  definite  regarding  the  nature 
of  the  process  of  salivary  secretion,  any  more  than  we  know 
regarding  the  forces  at  work  in  any  process  of  secretion. 
It  was  once  believed  that  the  saliva  represented  nothing 
but  a  filtrate  from  the  blood  which  was  squeezed  through 
the  gland-cells  under  the  influence  of  the  blood-pressure. 
This  idea  must  be  given  up  entirely,  for  the  chemical  com- 
position of  the  saliva  differs  from  that  of  blood-plasma 
or  lymph,  not  only  quantitatively  but  also  qualitatively. 
Certain  salts  are  present  in  greater,  others  in  less  amount 
than  in  the  blood,  and  while  some  chemical  constituents 
found  in  the  blood  do  not  appear  at  all  in  the  saliva,  the 
reverse  is  also  true.  We  must  therefore  conclude  that  the 
gland  cells  themselves  have  the  power  of  forming  new  chem- 


Till-:  REGULATION  OP  SALIVARY  SECRETION.      187 

ical  compounds  from  those  brought  them  in  bhe  blood,  and 
secondly  a  power  of  selection  in  that  they  lake  out  of  the 
blood  and  secrete  into  the  salivary  duels  only  certain  of 
the  constituents  of  the  blood-plasma.  How  little  the  blood- 
pressure  hi/  itself  is  of  any  importance  in  these  processes  of 
secretion  is  indicated  not  only  by  the  facts  already  cited, 
tliat  an  increase  in  blood-pressure  need  n<>(  be  followed  by 
an  increased  secretion  and  vice  versa,  but  also  by  Ludwig's 
classical  observation.  If  one  mercury  manometer  is  tied 
into  Wharton's  duct,  while  another  is  connected  with  the 
carotid  artery,  and  the  chorda  tympani  nerve  is  stimulated 
electrically  in  order  to  bring  about  a  secretion  of  saliva, 
the  pressure  registered  in  the  salivary  duct  may  be  100  to 
200  mm.  higher  than  that  in  the  arter}^.  It  is  possible  that 
osmotic  forces  brought  into  play  through  a  breaking  down 
of  complex  molecules  into  simpler  ones  may  explain  a  part 
of  the  phenomena  observed,  but  it  seems  much  more  prob- 
able that  the  great  pressures  produced  through  the  swelling 
of  colloids  (such  as  mucin)  in  water  are  chiefly  responsible. 
Not  only  are  colloids  having  a  great  affinity  for  water  pro- 
duced in  the  salivary  glands,  but  histological  evidence  is 
at  hand  to  indicate  that  during  secretion  those  portions  of 
the  gland-cells  lying  farthest  -  from  the  nucleus  suffer  the 
greatest  changes  in  size.  Since  the  nucleus  is  intimately 
connected  with  processes  of  intracellular  oxidation,  it  is 
conceivable  that  in  those  portions  of  the  cell  lying  nearest 
the  lumen  substances  are  formed  which  particularly  favor 
the  imbibition  of  water  by  the  colloids  formed  in  the  cells. 
In  this  way  the  cells  at  first  increase  in  size,  and  pres- 
sures are  produced  which  serve  to  squeeze  certain  por- 
tions of  the  cell  contents  (the  saliva)  into  the  glandular 
ducts.  Finally,  it  is  nol  impossible  thai  substances  capable 
of  swelling  may  be  secreted  into  the  smaller  salivary  duots 
and  that  the  pressures  registered  in  the  manometer  con- 
nected with  the  main  salivary  duct  may  be  due,  in  pari  at 
least,  to  the  subsequenl   swelling  cf  these  substances. 


CHAPTER  XI. 
THE  REGULATION  OF  GASTRIC  SECRETION. 

I.  Gastric  Fistulae. — For  our  earliest  knowledge  of  the 
secretion  of  gastric  juice  by  the  stomach,  and  its  qualitative 
and  quantitative  variations  under  different  physiological 
conditions,  we  are  indebted  to  the  American  physician  Beau- 
mont. Beaumont  made  his  observations  upon  the  hunter 
Alexis  St.  Martin,  who  retained,  in  consequence  of  a  gun- 
shot wound,  a  permanent  opening  in  the  abdominal  wall 
which  led  directly  into  the  stomach. 

An  attempt  to  reproduce  the  same  condition  of  affairs 
in  animals  led  to  the  experiments  of  more  modern  observers, 
who  created  gastric  fistulse  artificially  in  animals  of  various 
kinds.  The  results  obtained,  however,  were  by  no  means 
harmonious  or  satisfactory.  The  animals  sickened  and  died, 
or  at  the  best  secreted  a  juice"  which  was  evidently  subnor- 
mal, both  in  quantity  and  quality.  In  order  to  obtain  a 
flow  of  gastric  juice,  Beaumont  introduced  into  the  stomach 
of  his  patient  various  kinds  of  food.  The  students  of  gas- 
tric physiology  who  immediately  followed  him  used  the  same 
methods,  and  we  still  use  them  today  in  the  clinical  exam- 
ination of  the  gastric  juice.  A  patient  is  fed  a  specified 
diet  and  the  gastric  contents,  which  are  subsequently  re- 
moved through  introduction  of  a  stomach-tube,  are  sub- 
jected to  chemical  analysis.  This  procedure  does  not,  how- 
ever, yield  a  pure  juice,  but  one  mixed  with  food  particles, 
saliva,  etc. 

The  first  to  try  to  obtain  pure  gastric  juice  was  Klemen- 

188 


THE  REGULATION  OF  GASTRIC  SECRETION.        189 

si  i:\vicz,1  who  in  1875  followed  the  principle  adopted  byTinuv 
for  the  intestine,  and  attempted  the  isolation  of  a  part  of 
the  stomach  into  a  closed  pouch  which  opened  externally. 
His  dog  lived,  however,  only  three  days.  IIkimaii  aix  2  soon 
after  repeated  the  operation  and  succeeded  in  keeping  his 
animal  alive.  Pure  gastric  juice  can  be  obtained  from  a 
dog  operated  upon  in  this  way.  It  is  only  necessary  to 
introduce  food  into  the  large  stomach,  when  a  flow  of  per- 
fectly pure  gastric  juice  will  take  place  from  the  isolated 
cul-de-sac. 

The  operation  of  Heidenhain  possesses  the  important 
defect  of  interfering  with  the  nerve-supply  of  the  stomach. 
To  overcome  this  objection  Pawlow  and  Chigin  3  have 
devised  an  operative  procedure  which  will  be  described 
in  some  detail,  as  its  use  has  done  much  to  give  us  a  clearer 
insight  into  the  physiology  of  the  stomach.  An  incision  is 
made  into  the  stomach,  which  begins  in  the  fundus  a  little 
below  the  pylorus  and  runs  longitudinally  toward  the  car- 
dia.  This  incision  divides  both  anterior  and  posterior 
walls  (AB,  Fig.  20,  I).  The  triangular  flap  thus  formed 
is  made  into  a  cylinder,  the  orifice  of  which  is  sewed  into 
the  abdominal  wall,  while  its  base  is  still  connected  with 
the  main  cavity  of  the  stomach.  The  cavity  of  the  stomach 
and  that  of  the  pouch  do  not,  however,  communicate  with 
each  other,  but  are  separated  by  a  septum  of  mucous  mem- 
brane, as  indicated  in  Fig.  20,  II.  The  opening  in  the  main 
stomach  cavity  is  closed  by  a  line  of  sutures. 

In  order  to  obtain  gastric  juice  from  the  miniature  stomach 
(S,  Fig.  20,  II)  a  small  India  rubber  or  glass  tube,  freely 
perforated  at  its  lower  end,  is  introduced  through  the  opening 
in  the  abdominal  wall  (AA)  into  the  pouch.    The  tube  remains 

1  Klemensiewicz:  Sitzungsberichte  d.  Wiener  Akad.,  1N75,  Bd. 
LXXI. 

2  Heidenhain:  Pniiger's  Archiv.  1878,  XVIII,  p.  169. 

3  Pawlow  and  Chigin:  Pawlow's  Work  of  (he  Digestive  Glands. 
Translated  by  Thompson,  London,  1902,  p.  11. 


190 


PHYSIOLOGY  OF  ALIMENTATION. 
I 


Oesophagus 


Fig.   20. 

(Copied  from  PaWlow:   Work  of  the  Digestive  Glands.     Trans,   bj 

^Thompson,  London,  1902,  p.  12.) 


THE  REGULATION  OF  GASTRIC  SECRETION.        191 

in  the  pouch  of  its  own  accord,  or  may  be  fastened  there  by 
an  clastic  band  encircling  the  body  of  the  animal.  Juice  is 
collected  while  the  animal  is  lying  down  or  is  supported  in 
an  erect  position  in  a  suitable  frame. 

It  is  only  necessary  to  add  that  the  miniature  stomach 
gives  a  true  picture  of  the  secretory  activity  of  the  large  one 
(V),  even  though  food  does  not  at  all  enter  the  small  cavity. 
This  has  been  proved  by  a  long  series  of  carefully  conducted 
experiments,  in  which  the  quantity  and  quality  of  the  juice 
poured  out  in  the  large  cavity  has  been  compared  with 
that  poured  out  in  the  isolated  cul-de-sac. 

We  have  yet  to  describe  an  operative  procedure  which 
is  made  use  of  in  sham  feeding,  and  upon  which  several 
physiological  facts  concerning  the  stomach  and  its  activity 
are  based.  In  1889  Pawlow  and  Schumow-Simanowski 
performed  the  operation  of  oesophagotomy  on  a  dog  already 
possessing  a  simple  gastric  fistula.  The  oesophagus  is 
divided  in  the  neck,  and  the  divided  ends  are  made  to 
heal  separately  into  the  angles  of  the  skin  incision.  This 
separates  the  stomach  and  mouth  entirely.  Dogs  operated 
upon  in  this  way  recover  and  continue  in  excellent  health 
for  years  afterward.  To  keep  such  animals  alive,  food  must, 
of  course,  be  introduced  directly  into  the  stomach. 

The  following  experiment  shows  how  pure  gastric  juice 
can  be  obtained  from  such  an  animal.  If  the  dog  be 
given  meat  to  eat,  the  food  drops  out  again  from  the 
lower  extremity  of  the  upper  segment  of  the  divided  oesoph- 
agus. But  the  perfectly  empty  stomach  begins  to  secrete 
gastric  juice  and  this  continues  as  long  as  the  sham  feeding 
is  kept  up.  As  will  be  shown  in  detail  later,  this  is  a  psychic 
secretion  of  gastric  juice.  Suffice  it  for  the  time  being  to 
state  that  several  hundred  cubic  centimeters  of  pure,  gastric 
juice  may  be  obtained  daily  in  this  way  without  injury  to 
the  dog. 

CEsophagotomy  may  be  combined  with  the  already  de- 
scribed operation  of  Pawlow  and  Chigin  fur  the  separation 


192  PHYSIOLOGY  OF  ALIMENTATION. 

of  a  miniature  stomach  from  the  large.  This  and  other 
operative  variations  in  the  experiments  and  the  deductions 
which  may  be  drawn  from  them  are  given  below. 

2.  The  Effect  of  Diet  on  Gastric  Secretion. — The  experi- 
mental methods  of  Pawlow,  Schumow-Simanowski,  and 
Chigin  described  above  have  answered  for  us  a  number  of 
questions  connected  with  the  secretion  of  the  gastric  juice 
which  the  older  methods  could  only  hint  at.  Thanks  to  the 
ingenious  combination  of  an  cesophagotomy  with  a  simple  gas- 
tric fistula,  and  the  clever  surgical  procedure  which  allows  the 
separation  of  a  miniature  stomach  opening  externally  from 
the  main  stomach,  the  secretory  activity  of  this  organ  may 
be  followed  in  great  detail. 

The  stomach  of  the  fasting  animal  is  entirely  empty.  The 
secretion  of  gastric  juice  is  dependent  upon  the  taking  of 
food.  This  can  be  shown  very  nicely  in  a  dog  possessing  an 
isolated  miniature  stomach.  While  fasting,  this  is  entirely 
empty,  but  within  a  few  minutes  after  food  is  given  to  the 
animal  it  begins  to  secrete.  The  quantity  of  juice  secreted  is 
almost  exactly  proportional  to  the  amount  of  food  ingested. 
Chigin  gives  the  following  values  to  corroborate  this  state- 
ment: 

100  gms.  meat  26.0  c.c.  gastric  juice 

200     "         "  40.0  c.c.       "  " 

400     "         "  106.0  c.c.       " 

When,  instead  of  the  above,  various  amounts  of  a  mixed  diet 
made  up  of  meat  50  gms.,  bread  50  gms.,  milk  300  c.c.  are 
given,  the  same  fact  is  brought  out. 

The  above  mixture  yielded  42.0  c.c.  juice. 

Twice  the  above  mixture  yielded  83.2  c.c.  juice. 

The  gastric  secretion  is  not  all  poured  out  at  once  upon  the 
food,  but  continues  as  long  as  food  remains  in  the  stomach. 
The  rate  of  the  secretion  varies,  however,  from  hour  to  hour. 
The  secretion  reaches  its  maximum  within  the  first  hour, 


THE  REGULATION  OF  GASTRIC  SECRETION.        193 


after  which  it  decreases  steadily  in  amount  until  at  the 
end  of  a  number  of  hours  ii  has  fallen  to  the  zero-mark  once 
more.  The  cause  of  this  decrease  is  perhaps  explained  by 
the  gradual  den-cast"  in  the  amounl  of  food  undergoing  diges- 
tion in  the  stomach.  The  following  experiments  of  Chigin 
illustrate  the  above: 

Rate  of  Gastric  Secretion  after  Feeding  100  Cms.  Meat. 

Hour  after  feeding.  Quantity  of  juice  in  c.  c. 

Exp.  a.  Exp.  6. 

1  11.2  12.6 

2 
3 
4 
5 


These  values  are  represented  graphically  in  the  following 
curves  (Fig.  21). 


8.2 

8.0 

4.0 

2.2 

1.9 

1.1 

0.1 

a  drop 

Total. . . 

. .   25.4 

23.9 

HOUFu 

1 

2 

3 

4 

." 

1 

o 

d 

4 

5 

12 

10 

d 

d   8 

z 

•"    c 

O      () 

3 
—> 

4 

k 

n 

/ 

Fig.  21. — Curve  of  secretion  of  gastric  juice  after  a  meal  of  meat. 

Two  experiments. 

(Copied  from   I 'aw  low:     Work  of  t  lie   nicest  ive  ('.lands.      Trans,  by 

Thompson,  London,  L902,  p.  23.) 

Pawlow  and   Chigin's  miniature  stomach  allows  also  a 
study  of  the  qualitative  variations  in  the  gastric  juice  under 


194  PHYSIOLOGY  OF  ALIMENTATION. 

different  conditions  of  diet,  etc.  To  do  this  the  animal  is 
fed  in  the  ordinary  way,  and  the  secretion  which  pours  out  of 
the  miniature  stomach  is  collected,  measured,  and  used  for 
analysis.  It  was  pointed  out  above  that  the  secretions  of 
this  small  stomach  are  identical  with  those  of  the  large. 

The  following  table  indicates  how  the  digestive  power  of 
the  gastric  juice  varies  during  the  period  of  digestion,  after  a 
single  feeding  of  400  gms.  of  meat.1  The  cause  of  these 
variations  is  not  entirely  clear,  in  fact  their  very  existence 
is  questioned  by  some  observers.  The  digestive  power  is 
expressed  in  terms  of  millimeters  of  coagulated  egg-albumin 
digested  out  of  capillary  tubes  in  the  unit  of  time.  (Mett's 
method  of  determining  proteolysis  quantitatively.)2 

Hour  after  feeding.  Mm.  of  egg-albumin  digested. 

1 

2 
3 
4 
5 
6 
7 
8 

These  figures  are  plotted  in  the  form  of  curves  in  the  follow- 
ing illustration  (Fig.  22). 

The  digestive  power  of  the  gastric  juice,  which  Pawlow  and 
his  pupils  look  upon  as  an  expression  solely  of  the  amount  of 
ferment  (this  is  certainly  erroneous)  contained  in  the  juice, 
does  not  vary  with  the  amount  of  juice  secreted  in  the  unit 
of  time.  A  strong  digestive  power  may  be  found,  not  only 
when  the  secretion  is  scanty  but  also  when  it  is  copious. 

So  far  as  the  inorganic  constituents  of  the  gastric  juice  are 
concerned,  Pawlow  believes  that  the  concentration  of  hydro- 

1  Lobassoff:  Pawlow'  s  Work  of  the  Digestive  Glands.  Translated 
by  Thompson,  London,  1902,  p.  29, 

2  See  p.  130. 


Exp.  a 

Exp.  b. 

6.0 

5.8 

4.3 

4.1 

3.4 

3.4 

3.5 

3.0 

3.8 

3.8 

3.0 

3.1 

3.6 

3.5 

3.9 

4.5 

THE   REGULATION   OF  GASTRIC  SECRETION. 


105 


chloric  acid  never  varies.  This  applies,  however,  only  to  the 
gastric  juice  as  it  is  poured  out  by  the  glands.  Once  the  juice 
has  left  the  crypts  of  the  gastric  mucosa,  its  acidity  may  be 
reduced  through  various  agencies,  and  it  is  to  these  that  the 
fluctuations  in  the  acidity  of  the  gastric  juice  under  various 
physiological  and  pathological  conditions  must  be  attributed. 
The  mucus  secreted  by  the  stomach-wall  has  the  power  of 
neutralizing  the  acid  of  the  gastric  juice.     For  this  reason 


RS 

0.0 
5.0 

}          :?          4 

'>          0 

8 

12          3          4 

I 

>          G 

B 

i 

L0 

8.0 

2.0 

1.0 

il 


Fig.  22. — Digestive  power  of  hourly  portions  of  gastric  juice  after  a 

meal  of  400  gms.  of  meat. 
(Copied  from  Pawlow:    Work  of  the  Digestive  Glands.     Trans,  by 
Thompson,  London,  1902,  p.  28.) 

the  first  juice  collected  from  the  stomach  of  a  fasting  dog 
always  has  a  lower  acidity  than  later  specimens,  for  the 
empty  stomach  is  covered  with  a  layer  of  mucus.  Also,  the 
more  rapidly  gastric  juice  is  secreted  the  higher  is  its  acidity, 
for  in  this  way  less  time  is  allowed  for  the  neutralization  of 
the  hydrochloric  acid  through  the  gastric  mucus.  Finally, 
the  power  of  the  saliva  which  enters  the  stomach  to  neu- 
tralize the  acid  secreted  there  must  also  be  borne  in  mind. 

The  gastric  juice  poured  out  upon  different  kinds  of  food 
varies  not  only  in  quantity  but  also  in  quality.  The  ex- 
periments of  some  of  the  older  observers  lend  support  to 
this  idea,  but  their  results  cannot  be  looked  upon  as  en- 
tirely free  from  criticism.     The  results  of  Pawlow  and  his 


JUICE  IN  c.c. 


p- 

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2  s. 

A  P 


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p 

THE  REGULATION  OF  GASTRIC  SECRETION.        1^7 


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MM.  OF    PROTEIN  COLUMN 


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198  PHYSIOLOGY  OF  ALIMENTATION. 

pupils  are  perhaps  more  trustworthy.  The  average  variation 
in  the  ferment  content  (better  digestive  power)  of  the  juices 
poured  out  when  equal  weights  of  bread,  meat,  or  milk  are 
fed,  expressed  in  terms  of  millimeters  of  coagulated  egg- 
albumin  digested  out  of  capillary  tubes  in  the  unit  of  time, 
is  shown  in  the  following  table: 

Bread  6 .  64  mm. 
Meat  3.99mm. 
Milk     3.26  mm. 

Since  the  amount  of  proteolytic  ferment  contained  in 
the  compared  juices  is  proportional  to  the  square  of  the 
rapidity  of  digestion,  we  find  upon  calculation  that  the  juice 
poured  out  upon  bread  contains  four  times  as  much  acid- 
proteinase  as  that  poured  out  upon  milk  and  about  three 
times  as  much  as  that  poured  out  upon  meat,  for  the  squares 
of  the  figures  given  in  the  above  table  stand  as  44:16:11. 

The  quantitative  variation  in  the  secretion  of  the  gastric 
juice  (expressed  in  cubic  centimeters)  when  different  foods 
are  given  is  indicated  in  the  following  experiment  of  Chigin; 
the  digestive  power  of  the  juices  (expressed  in  millimeters 
of  digested  egg-albumin)  is  given  in  the  parentheses  follow- 
ing these  values. 

Quantity  and  Quality  of  Gastric  Juice  Seceeted  upon  Feeding. 

Hour.  200  gms.  meat.  200  gms.  bread.  600  c.c.  milk. 


1 

11.2(4.94) 

10.6(6.10) 

4.0(4.21) 

2 

11.3(3.03) 

5.4(7.97) 

8.6(2.35) 

3 

7.6(3.01) 

4.0(7.51) 

9.2(2.35) 

4 

5.1  (2.87) 

3.4(6.19) 

7.7(2.65) 

5 

2.8(3.20) 

3.3(5.29) 

4.0(4.63) 

6 

2.2(3.58) 

2.2(5.72) 

0.5(6.12) 

7 

1.2(2.25) 

2.6(5.48) 

...(..    .) 

8 

0.6(3.87) 

2.6(5.50) 

...(....) 

9 

...(....) 

0.9(5.75) 

...(....) 

10 

...(....) 

0.4(....) 

...(....) 

The  values  are  represented  graphically  in  Figs.  23  and  24. 
Each  kind  of  food  seems  to  bring  about  a  definite  hourly 


THE  REGULATION  OF  GASTRIC  SECRETION.        199 

rate  of  secretion  and  a  characteristic  alteration  in  the  prop- 
erties of  the  juice.  With  a  meat  diet  the  maximum  rate 
of  secretion  occurs  during  the  first  or  second  hour,  during 
which  periods  the  quantity  of  juice  secreted  is  approxi- 
mately the  same.  With  bread  the  maximum  secretion 
occurs  during  the  first  hour,  while  with  milk  it  occurs  dur- 
ing the  second  or  third  hour.  The  juice  has  the  greatest 
digestive  power  during  the  first  hour  when  meat  is  fed, 
during  the  second  and  third  when  bread  is  given,  and  during 
the  last  hour  when  milk  is  the  food  furnished  the  dog. 

As  the  gastric  juice  acts  chiefly  upon  the  protein  con- 
stituent of  the  food,  Pawlow  has  made  an  interesting  cal- 
culation of  the  comparative  work  done  by  the  stomach  in 
digesting  the  three  articles  of  food  mentioned  above,  taking 
into  consideration  the  nitrogen  content  of  the  foods  and  the 
quality  and  quantity  of  gastric  juice  poured  out  upon  them. 
He  finds  that  the  number  of  ferment  units  (obtained  by 
multiplying  the  squares  of  the  numbers  representing  the 
digestive  strengths  by  the  number  of  c.c.  poured  out  upon 
the  food)  required  for  the  digestion  of  corresponding  nitro- 
gen equivalents  in  the  different  kinds  of  food  is  as  follows: 

Bread  1600  units 
Meat      430       " 
Milk       340       " 

This  means  that  protein  in  the  form  of  bread  requires 
five  times  more  acid-proteinase  for  its  digestion  than  is 
poured  out  upon  the  same  amount  of  protein  in  milk,  and 
that  the  protein  of  meat  requires  a  fourth  more  than  its 
equivalent  contained  in  milk.  Now  it  is  known  that  vege- 
table proteins  are  much  less  easily  digested  than  those  of 
meat,  and  these  less  than  those  of  milk.  The  different 
kinds  of  proteins  seem,  therefore,  to  call  forth  the  secretion 
of  quantities  of  ferment  which  correspond  with  the  differ- 
ences in  their  digestibility. 

The  concentration  of  the  hi/drochloric  acid  in  the  gastric 
juice  also  varies  with  the  different  kinds  of  food.      It    is 


200  PHYSIOLOGY   OF  ALIMENTATION. 

greatest  when  meat  is  fed  (0.56  percent  HC1)  and  lowest 
when  bread  is  given  (0.46  percent  HC1).  A  milk  diet  gives 
an  intermediate  figure. 

3.  The  Relation  of  the  Nervous  System  to  Gastric  Secre- 
tion.— The  relation  of  the  nervous  system  to  the  secretion 
of  the  gastric  juice  by  the  stomach  has  for  many  years  been 
the  subject  of  debate.  Against  the  well-known  clinical 
fact  that  emotional  states,  injuries  of  various  kinds,  etc., 
profoundly  alter  the  activity  of  the  stomach  stood  the 
observations  of  a  score  of  experimenters  who  were  able  to 
prove  no  direct  connection  between  the  central  nervous 
system  and  the  digestive  organ.  In  1852  Bidder  and 
Schmidt  published  the  fact  that  the  mere  sight  of  food 
will  call  forth  a  secretion  of  gastric  juice  in  the  dog,  and 
in  1878  Richet  demonstrated  on  a  patient  gastrotomized 
for  an  incurable  stricture  of  the  oesophagus  that  a  secre- 
tion of  gastric  juice  occurred  whenever  the  patient  took 
certain  articles  of  food  into  the  mouth.  The  efforts,  how- 
ever, to  show  the  paths  of  nervous  connection  in  these  cases 
were  singularly  unsuccessful.  In  recent  years,  however, 
Pawlow  and  his  coworkers  Schumow-Simanowski,  Jur- 
gens,  and  Ssanozki,  in  a  series  of  beautiful  experiments, 
have  been  more  fortunate,  and,  thanks  to  their  researches, 
we  are  now  familiar  with  the  cause  of  failure  in  the  older 
experiments,  and  may  look  upon  the  connection  between 
central  nervous  system  and  stomach  as  experimentally 
proved  and  the  nervous  paths  constituting  this  connection 
as  fundamentally  established. 

The  following  experiment  shows  that  the  effect  of  feeding 
is  transmitted  to  the  gastric  glands  through  nervous  channels 
and  that  one  of  these  channels  is  the  vagus  nerve.1  A  dog, 
possessing  an  ordinary  gastric  fistula  and  cesophagotomized 
as  described  above,2  so  that  the  mouth  is  entirely  cut  off 

'Pawlow:  Work  of  the  Digestive  Glands.     Translated  by  Thomp- 
son, London, 1902,  p.  50. 
2  See  p.  191. 


THE  REGULATION  OF   (iASTUIC  SECRETION.        201 

from  communication  with  the  stomach,  is  used.  In  addi- 
tion the  right  vagus  nerve  is  divided  below  the  recurrent 
laryngeal  and  cardiac  branches,  at  Hie  lime  that  the 
gastric  fistula  is  made.  No  juice  (lows  from  the  gastric 
fistula  in  such  a  dog.  If  now  sham  feeding  is  indulged 
in,  that  is  to  say  if  the  dog  is  fed  food  which  it  swallows 
but  which  never  reaches  the  stomach,  because  the  swallowed 
masses  drop  out  of  the  oesophageal  opening  in  the  neck, 
a  stream  of  gastric  juice,  which  steadily  increases  in  volume, 
appears  at  the  gastric  opening  within  five  minutes  after 
the  dog  is  given  its  first  food.  As  long  as  the  dog  is  fed, 
which  may  be  two  or  more  hours,  often  even  five  or  six, 
the  gastric  juice  continues  to  pour  out  of  the  fistula.  In 
this  way  several  hundred  cubic  centimeters  of  juice  may 
be  collected. 

How  is  this  effect  of  feeding  carried  from  the  mouth  to  the 
stomach?  If  the  food  is  taken  away  from  the  dog  in  the 
experiment  just  described,  the  secretion  of  gastric  juice  con- 
tinues for  several  hours,  gradually  becoming  less  in  quantity. 
The  right  vagotomy  threw  out  of  function  only  the  pulmon- 
ary and  abdominal  branches  on  the  side  operated  upon  while 
the  laryngeal  and  cardiac  fibres  were  left  intact.  If  now  the 
left  vagus  nerve,  wdiich  has  been  laid  free  in  the  neck  by 
operation  some  three  hours  before  the  sham  feeding  is  to  be 
indulged  in,  be  carefully  drawn  out  of  the  wound  and  divided 
with  a  snip  of  the  scissors,  the  pulmonary  and  abdominal 
branches  of  both  vagi  are  paralyzed.  The  preservation  of 
the  laryngeal  and  cardiac  fibres  on  the  right  side,  however, 
prevents  the  symptoms  of  cardiac  and  laryngeal  distress 
which  follow  division  higher  in  the  neck.  If  food  be  now 
given  this  dog  a  second  time,  it  eats  greedily  as  before,  but,  in 
sharp  contrast  to  the  preceding  sham  feeding,  not  a  single 
drop  of  gastric  juice  Hows  from  the  stomach.  Indeed,  never 
again  in  such  a  double  vagotomized  dog,  even  if  it  lives  for 
months  afterwardj  as  some  of  (hem  do,  docs  a  sham  feeding 
call  forth  a  secretion  of  gastric  juice. 


202  PHYSIOLOGY  *OF  ALIMENTATION. 

When  sham  feeding  no  longer  produces  a  secretion  of  gastric 
juice  after  double  vagotomy,  it  does  not  mean,  however,  that 
the  gastric  glands  have  lost  the  power  of  secretion.  As  will 
be  shown  later,  highly  active  juice  can,  under  appropriate 
circumstances,  still  be  obtained  from  this  digestive  organ. 
The  above  experiment  only  shows  that  certain  exciting  in- 
fluences which  normally,  in  the  ordinary  process  of  eating, 
reach  the  gastric  mucosa  by  way  of  the  vagi  have  been 
removed.  As  has  been  shown  by  Ketscher,  the  mode  of 
feeding  and  the  character  of  the  food  presented  to  the  dog 
during  sham  feeding  alters  markedly  the  character  of  the 
gastric  juice  obtained.  If  the  dog  is  given  pieces  of  meat  at 
long  intervals,  less  gastric  juice  and  one  lower  in  digestive 
power  is  obtained  than  when  the  dog  is  fed  more  rapidly. 
In  a  similar  manner,  a  diet  of  meat,  which  the  dog  relishes 
highly,  produces  more  juice  and  one  having  a  higher  digestive 
power  than  a  meal  of  bread,  which  the  dog  relishes  less. 

The  existence  of  nerve  fibres  in  the  vagus  which  influence 
the  secretion  of  gastric  juice  was  proven  above  by  showing 
that  after  division  of  both  vagi  stimulation  of  the  buccal 
cavity  with  food  no  longer  excited  the  gastric  mucosa  to 
activity  as  before.  It  can,  however,  be  shown  by  direct 
stimulation  of  the  vagus  in  a  properly  performed  experiment, 
that  this  nerve  contains  fibres  which  influence  the  activity 
of  the  stomach.  This  has  been  accomplished  by  Pawlow  and 
Schumow-Simanowski.  A  gastrotomized  and  cesophagot- 
omized  dog,  in  which  the  right  vagus  nerve  has  been  cut  below 
the  origin  of  the  inferior  laryngeal  and  cardiac  fibres,  is  used 
for  the  experiment.  Three  or  four  days  before  stimulation 
of  the  vagus  is  to  be  carried  out,  the  left  vagus  is  carefully 
dissected  out  in  the  neck,  a  ligature  passed  around  it  but  not 
tied,  and  the  whole  carefully  preserved  under  the  skin.  On 
the  day  the  vagus  stimulation  is  to  be  carried  out,  the  wound 
is  painlessly  opened  and  the  nerve  laid  bare.  By  attending 
to  these  details,  whereby  appreciable  pain  to  the  animal  is 
avoided,  excitation  of  the  vagus  by  induction  shocks  at  in- 


THE  REGULATION  OF  GASTRIC  SECRETION        203 

tervals  of  one  or  two  seconds  invariably  yields  a  secretion  of 
gastric  juice  from  the  stomach.  The  negative  or  at  best 
uncertain  results  of  the  older  observers  upon  stimulation 
of  the  vagus  are  probably  all  to  be  explained  by  the  fact  thai 
their  animals  were  under  the  influence  of  anaesthetics  or  in 
pain,  and,  as  will  become  apparent  when  the  pancreatic 
secretion  is  described,  peripheral  stimuli  of  various  kinds 
inhibit  markedly  the  activity  of  the  digestive  glands.  When 
all  peripheral  stimuli  are  prevented  from  inhibiting  reflexly 
the  activity  of  the  stomach  (this  can  be  done  by  dividing  the 
spinal  cord  just  below  the  medulla  oblongata),  the  vagus 
nerves  ma)'  be  laid  bare  in  the  neck  and  stimulated  at  once, 
when  a  secretion  of  gastric  juice  will  be  observed.  In  this 
way  Uschakoff  has  succeeded  in  demonstrating,  in  an  experi- 
ment performed  at  one  sitting,  the  relation  of  the  vagus  nerve 
to  the  stomach. 

Both  forms  of  experiment,  the  "chronic  "  as  well  as  the 
"acute,"  show,  therefore,  that  the  vagus  nerve  contains  fibres 
which  influence  the  secretion  of  the  gastric  glands.  As  will 
be  shown  later,  however,  a  secretion  of  gastric  juice  occurs 
also  when  the  vagi  are  cut;  this  indicates  that  the  integrity 
of  the  vagus  is  not  the  only  requisite  for  the  secretory  activity 
of  the  stomach.  Under  normal  circumstances,  however,  these 
nerves  play  the  already  described  exceedingly  important  role 
in  the  initiation  of  the  gastric  flow. 

4.  The  Appetite  as  an  Excitant  of  Gastric  Secretion. — 
It  was  shown  in  the  preceding  paragraphs  that  the  vagus 
nerve  has  a  marked  influence  upon  the  secretion  of  juice  by 
the  stomach.  We  have  now  to  answer  the  question,  How 
is  the  vagus  nerve  normally  excited?  An  explanation  which 
first  suggests  itself  is  that  we  are  dealing  with  a  reflex  excita- 
tion of  the  gastric  mucosa,  brought  about  through  a  stimula- 
tion of  nerve  endings  in  the  mouth  and  carried  from  here  to 
the  vagus  centre  in  the  medulla,  and  from  there  down- 
ward to  the  stomach.  This  idea  has  been  carefully  tested 
experimentally  by  PAWLOwand  found  to  be  incorrect,  as  shown 


204  PHYSIOLOGY  OF  ALIMENTATION. 

by  the  following  facts.  The  food  upon  entering  the  mouth  is 
able  to  stimulate  the  buccal  mucous  membrane,  either  chem- 
ically, mechanically,  or  in  both  of  these  ways.  Application 
of  such  substances  as  acids,  salts,  bitters,  pepper,  mustard, 
etc.,  to  the  mucous  membrane  of  an  cesophagotomized  dog 
never  calls  forth  a  secretion  of  gastric  juice,  however.  Not 
even  does  a  meat  decoction  in  most  instances  prove  effective 
in  this  regard.  Nor  does  a  combination  of  mechanical  stimu- 
lation with  the  chemical,  such  as  wiping  out  the  mouth  with 
an  acid-soaked  sponge,  or  giving  the  dog  stones  to  swallow, 
work  any  more  successfully  in  exciting  the  gastric  mucous 
membrane.  The  stones  drop  out  of  the  oesophagus,  and, 
even  if  this  play  is  kept  up  for  hours,  not  a  drop  of  gastric 
juice  flows  from  the  gastric  fistula.  As  soon,  however,  as 
the  old  experiment  of  sham  feeding  is  tried,  and  meat  or  bread 
is  given  the  dog  instead  of  stones,  a  free  flow  of  gastric  juice 
begins  in  five  minutes  and  steadily  increases  in  amount  as 
described  above.  These  facts  prove  clearly  that  the  nerves 
of  the  stomach  are  not  excited  reflexly  through  chemical  or 
mechanical  stimulation  of  the  buccal  mucous  membrane. 
Wherein  then  does  the  sham  feeding  with  food  differ  from 
that  with  stones?  In  the  former  case  the  dog  eagerly  de- 
sires its  meal,  something  which  is  lacking  in  the  latter.  This 
eager  desire  for  food,  the  appetite  in  other  words,  is  the  excitant 
of  the  gastric  flow,  and  we  must  conclude  in  consequence  that 
a  psychic  state  rather  than  a  reflex  from  the  mouth  acts  as 
the  normal  excitant  of  the  vagus  nerve  and  the  gastric  mucosa 
at  the  beginning  of  a  meal. 

Bidder  and  Schmidt  observed  years  ago  that  merely  offer- 
ing a  hungry  dog  food  excited  a  flow  of  gastric  juice.  Paw- 
low  has  confirmed  and  elaborated  this  experimental  finding. 
Actual  sham  feeding  with  food  does  not  need  to  be  indulged 
in  in  order  to  obtain  a  flow  of  gastric  juice.  If  only  a  tempting 
meal  be  prepared  before  a  hungry  dog,  a  flow  of  gastric  juice, 
such  as  has  been  described  when  sham  feeding  is  practised, 
begins  within  five  minutes  after  the  teasing  is  begun.     In 


THE  REGULATION  OF  GASTRIC  SECRETION.       205 

fact  it  has  been  shown  experimentally  by  Ssanozki  that 
merely  tempting  a  dog  with  food  often  leads  to  a  greater  secre- 
tion of  gastric  juice  in  the  unit  of  time  than  the  actual  sham 
feeding. 

The  "appetite  juice"  varies  both  in  quantity  and  quality. 
The  more  eagerly  a  dog  eats  the  greater  the  amount  of  juice 
and  the  higher  the  digestive  power.  A  good  appetite  at  the 
beginning  of  a  meal  is,  therefore,  equal  to  a  copious  secre- 
tion of  strong  gastric  juice. 

5.  The  Physiological  Importance  of  the  Appetite  Juice. — 
It  was  shown  above  that  the  secretion  of  gastric  juice  during 
the  first  hour  is  practically  the  same  for  meat  or  bread,  and 
that  only  subsequently  the  amount  and  quality  of  the  gastric 
secretion  varies  with  the  nature  of  the  ingested  food.  When 
only  sham  feeding  with  these  same  foods  is  indulged  in,  we  find 
that  the  secretion  of  juice  for  the  first  hour  is  the  same  as 
though  the  dog  had  been  actually  fed.  All  this  indicates 
that  the  first  outpouring  of  juice  into  the  stomach  at  the 
beginning  of  a  meal  is  the  consequence  of  the  psychic  excita- 
tion. The  truth  of  this  statement  is  still  further  borne  out 
by  the  fact  that  when  a  food  is  given  the  dog  which  does  not 
interest  him  to  the  same  degree  as  meat  or  bread, — for  example, 
milk, — this  initial  rise  in  the  quantity  and  quality  of  the  gas- 
tric juice  does  not  appear.  While  12.4  c.c.  of  gastric  juice, 
having  a  digestive  power  of  5.43  mm.,  are  poured  out  upon 
meat,  and  13.4  c.c,  having  a  digestive  power  of  5.37  mm., 
are  poured  out  upon  bread  during  the  first  hour  after  feeding, 
only  4.2  c.c.  of  a  digestive  power  of  3.57  mm.  are  poured  out 
upon  milk  (Chigin).  That  the  mere  act  of  taking  food  in- 
creases both  the  quantity  and  quality  of  the  gastric  juice 
is  still  further  supported  by  the  observation  of  Kotljar  and 
Lobassoff,  who  found  that  when  an  ordinary  meal  is  divided 
into  several  portions,  and  these  are  fed  at  intervals  of  three 
hours,  an  increase  in  the  quantity  and  quality  of  the  juice 
immediately  follows  each  installment. 

The  role  of  the  appetite  juice  can  be  still  more  clearly 


206 


PHYSIOLOGY  OF  ALIMENTATION 


Hours  after  feeding 
2  3 


12 


10 


6  8 


2  6 


11| 

ti 


A  B 

Fig.  25. 

A = ordinary  curve  of  gastric  secretion. 

B=  curve  from  direct  introduction  of  food  into  stomach. 

demonstrated  by  comparing  gastric  digestion  in  which  it  is 
allowed  to  play  a  part,  with  gastric  digestion  in  which  the 
psychic  element  is  shut  out.  This  can  be  readily  done  in  an 
cesophagotomized  dog  which  possesses  a  fistula  leading  into 
the  main  stomach  in  addition  to  having  a  gastric  cul-de-sae. 
If  food  is  introduced  into  such  a  dog's  main  stomach 
without  attracting  its  attention,  it  is  found  that  digestion 
goes  on  at  an  entirely  different  rate  than  when  the  psy- 
chic element  is  allowed  to  play  a  part.  Under  these  cir- 
cumstances, bread  and  coagulated  white  of  egg  do  not  yield 


THE  REGULATION  OF  GASTRIC  SECRETION.       207 
12  3  1  2  :;  4 


Fig.  25. 

C= curve  from  sham  feeding. 
D= summation  of  B  and  C . 
(Copied  from  Pawlow:  Work  of  the  Digestive  Glands. 
Thompson,  London,  1902,  p.  82.) 


Trans,  by 


a  single  drop  of  juice  for  an  hour  or  more  afterward  and  the 
introduction  of  meat  yields  a  gastric  secretion  only  after  a 
considerable  period  of  delay.  It  begins  in  the  latter  case  in 
15  to  45  minutes  after  feeding,  instead  of  6  to  10  minutes  as 
normally,  and  when  it  does  flow  is  poorer,  both  in  quantity 
and  quality,  than  under  normal  circumstances.  In  the  accom- 
panying figure  (Fig.  25),  curve  .1  shows  the  ordinary  course 
of  gastric  secretion  following  a  meal  of  200  gms.  of  meat; 


208  PHYSIOLOGY  OF  ALIMENTATION. 

curve  B  that  obtained  when  the  same  amount  of  food  is 
introduced  into  the  stomach  directly,  and  curve  C  the  result 
when  sham  feeding  with  the  same  is  indulged  in.  D  is  a 
synthetic  curve  produced  by  adding  B  and  C  and  approxi- 
mates closely  curve  A.  As  can  readily  be  seen,  the  introduc- 
tion of  food  into  the  stomach  directly  does  not  lead  to  as  rapid 
or  as  great  a  secretion  of  gastric  juice  as  does  the  normal 
process  of  feeding.  But  if  the  quantities  obtained  by  intro- 
ducing the  meat  into  the  stomach  be  added  to  those  ob- 
tained by  sham  feeding  a  curve  almost  identical  with  the 
normal  results. 

The  importance  of  the  psychic  element  in  gastric  digestion 
can  be  demonstrated  still  more  strikingly  by  the  following  ex- 
periment of  Lobassoff  on  two  cesophagotomized  dogs  pos- 
sessing ordinary  gastric  fistulse.  If  a  definite  number  of 
pieces  of  meat  threaded  on  strings  be  introduced  directly  into 
the  stomach  of  one  dog  while  its  attention  is  being  distracted 
by  patting  and  talking  kindly  to  it,  and  an  equal  number  of 
pieces  are  introduced  into  the  stomach  of  another  dog,  but 
during  the  process  a  vigorous  sham  feeding  is  kept  up,  the 
following  differences  are  noted.  Two  hours  after  25  pieces 
weighing  100  gms.  in  all  had  been  fed  to  each  of  the  dogs, 
the  dog  without  sham  feeding  had  digested  6.5  percent, 
the  one  with  sham  feeding  for  eight  minutes,  31.6  percent, 
as  shown  by  subsequent  weighing  of  the  undigested  food  ex- 
tracted from  the  stomach.  In  another  experiment,  in  which 
the  meat  had  remained  for  five  hours  in  the  stomachs,  58 
percent  had  been  digested  without  sham  feeding,  while. 85 
percent  had  been  digested  with  sham  feeding.  These  figures 
leave  no  room  for  doubt  of  the  great  importance  to  be  attached 
to  the  eager  desire  for  food,  in  other  words  to  the  appetite. 

6.  Other  Excitants  of  Gastric  Secretion. — It  must  not 
be  believed  from  the  foregoing  that  the  appetite  is  the  only 
excitant  of  gastric  secretion.  This  is  shown  not  only  by 
the  observation  that  a  secretion  of  gastric  juice  occurs  when 
the  psj^chic   element  is  allowed  to  play  no  part  at  all,  as 


THE  REGVLAT10S  OF  GASTRIC  SECRETION.       2()9 

when  the  food  is  introduced  into  the  stomach  directly,  but 
also  by  the  fact  that  the  effect  of  sham  feeding  does  not  last 
as  long  as  an  ordinary  digestive  period  nor  yield  in  the  later 
hours,  of  this  period  as  active  a  juice  as  is  obtained  after  a 
true  meal.  What,  then,  are  the  other  excitants  of  the  gastric 
How  besides  the  appetite  which  we  have  seen  above  plays  so 
important  a  role  in  digestion?  We  think  naturally  of  the 
mechanical  stimulation  and  secondly  of  the  chemical  stimu- 
lation which  might  be  brought  about  by  the  presence  of  the 
food  in  the  stomach.  Let  us  first  see  if  mechanical  stimu- 
lation is  effective  in  bringing  about  a  secretion  of  gastric 
juice  from  the  stomach. 

Almost  without  exception  the  older  observers  believed  that 
mechanical  stimulation  of  the  gastric  mucosa  by  a  feather 
or  a  glass  rod  would  yield  at  least  some  secretion  of  gastric 
juice.  Within  recent  years,  however,  this  question  has  been 
investigated  by  Pawlow  and  his  coworkers,  who  have  pointed 
out  the  sources  of  error  in  the  older  experiments,  and  today 
we  say  that  mechanical  stimulation  is  ineffective  in  bringing 
about  a  secretion  of  gastric  juice.  This  is  shown  by  the  follow- 
ing experiment.1 

In  an  oesophagotomized  dog  possessing  a  gastric  fistula 
the  stomach  is  first  thoroughly  washed  out  with  water.  If 
the  mucous  membrane  is  now  mechanically  stimulated  by 
moving  a  feather  or  a  glass  rod  over  it  continuously  for  a 
half  hour  or  more,  or  if  a  stream  of  fine  sand  is  blown  against 
it,  or  finally,  if  the  stomach  is  distended  to  the  size  of  a  child's 
head  by  inserting  within  it  a  rubber  ball,  not  a  single  drop  of 
gastric  juice  is  discharged.  Only  a  little  mucus  which  turns 
red  litmus  paper  blue  may  be  expelled.  But  let  sham  feed- 
ing with  bread  or  meat  be  carried  out  upon  the  same  dog,  and 
an  acid  juice  appears  within  five  or  ten  minutes  after  the 
beginning  of  the  feeding.     The  older  observers  never  obtained 


1  Pawlow:  Work  of  the  Digestive  Glands.     Translated  by  Thomp- 
son, London,  1902,  p.  86. 


210  PHYSIOLOGY  OF  ALIMENTATION. 

through  mechanical  stimulation  a  gastric  juice  which  even 
approximated  the  acidity  obtained  by  sham  feeding.  That 
they  obtained  any  acid  secretion  at  all  is  due  to  errors  in 
experiment,  such  as  not  washing  out  the  stomach  properly, 
not  waiting  until  the  stimulation  to  gastric  secretion  from  the 
previous  meal  had  entirely  worn  off,  or  causing  a  psychic 
secretion  of  the  gastric  juice  by  exciting  the  dog  through  the 
smell  of  food  on  the  hands,  the  appearance  of  the  attendant 
who  usually  fed  the  dog,  etc. 

Having  settled  now  that  the  mechanical  properties  of  the 
food  are  in  themselves  unable  to  call  forth  a  secretion  of  gas- 
tric juice  we  turn  to  its  chemical  properties.  What  chemical 
constituents  of  the  food  bring  about  a  secretion  of  juice  from 
the  stomach?  In  order  to  investigate  this  problem  a  dog 
with  a  miniature  stomach,  and  possessing  in  addition  a  fistula 
passing  into  the  main  cavity,  can  best  be  used.  The  food 
undergoing  study  is  introduced  into  the  main  cavity,  and  the 
amount  and  quality  of  the  juice  which  flows  from  the  isolated 
cul-de-sac  examined.  In  order  not  to  bring  about  a  psychic 
secretion  of  the  gastric  juice,  it  is  best  to  introduce  the  food 
while  the  dog  is  asleep,  or  while  the  dog's  attention  is  dis- 
tracted from  what  is  going  on  if  the  animal  is  awake. 

Water,  first  of  all,  has  an  exciting  effect  upon  the  gastric 
glands.  It  has  been  found  by  Chigin  that  when  400  to  500 
c.c.  of  water  are  introduced  into  the  large  stomach  of  a  dog, 
a  small  but  constant  secretion  of  juice  occurs  from  the  lesser 
one.  This  fact  had  been  previously  found  by  Heidenhain. 
Smaller  quantities  of  water  are  not  so  effective,  and  if  only 
100  to  150  c.c.  are  injected  into  the  large  stomach,  usually 
no  secretion  of  juice  at  all  occurs.  The  results  are  the  same 
when  before  the  introduction  of  the  water  the  vagi  nerves 
are  divided  below  the  diaphragm  or  in  the  neck. 

Neither  solutions  of  sodium  chloride,  sodium  bicarbonate,  or 
hydrochloric  acid  excite  a  flow  of  gastric  juice.  According  to 
Chigin  0.05  to  1  percent  sodium  bicarbonate  solutions,  when 
introduced  in  the  same  amounts  as  proved  effective  when 


THE  REGULATION   OF  GASTRIC   SECRETION.       211 

water  alone  was  injected,  bring  about  not  even  a  slight  secre- 
tion of  gastric  juice.  This  salt  is,  therefore,  to  be  looked 
upon  as  inhibiting  the  gastric  flow,  for  its  presence  prevents 
the  usual  exciting  effects  of  the  water  alone.  Oils  also  have 
a  distinct  inhibitory  effect,  according  to  Lobassoff. 

Uncoagulated  white  of  egg,  whether  diluted  with  water  or 
not,  never  brings  about  a  greater  secretion  of  gastric  juice 
than  the  same  volume  of  pure  water.  This  is  an  altogether 
unexpected  fact,  and  points  to  the  importance  of  the  appetite 
juice  in  normal  digestion.  Neither  does  starch,  boiled  or  un- 
boiled and  variously  diluted,  nor  grape-sugar,  nor  cane-sugar, 
excite  the  stomach  to  secrete  juice.  Even  bread  and  boiled 
white  of  egg  remain  for  hours  in  the  stomach  and  excite  no 
gastric  secretion  if  the  psychic  element  is  shut  out. 

Certain  commercial  peptones  will  excite  the  gastric  mucous 
membrane  directly,  but  by  no  means  all  of  them.  Pure 
peptones  do  not,  however,  have  this  effect.  We  are  in 
consequence  driven  to  the  conclusion  that  the  commercial 
peptones  contain  as  yet  unknown  chemical  substances 
which  are  the  real  excitants  of  the  gastric  flow.  Meat  broth, 
meat  juice,  and  solutions  of  meat  extract  act  as  constant  and 
active  excitants  of  the  gastric  secretion.  Meat  also  belongs 
in  this  group,  but  all  these  substances  bring  on  a  flow  of  gas- 
tric juice  much  later  than  when  sham  feeding  is  practised. 
Whereas  the  latter  method  shows  a  beginning  of  secretion 
after  5  minutes,  the  former  is  without  effect  for  15  to  45 
minutes  afterward.  The  majority  of  foodstuffs  does  not, 
therefore,  affect  the  secretion  of  gastric  juice.  To  the 
minority  which  is  active  in  this  direction,  water  and  cer- 
tain as  yet  unknown  constituents  of  meat  belong.  The 
manner  in  which  these  are  effective  is  now  to  be  discussed. 

7.  Gastric  Secretin. — When  we  study  the  quantitative 
variations  in  the  secretion  of  gastric  juice,  we  note  that 
the  curve  of  secretion  shows  two  maximal  points.  The  first 
of  these  is  observed  immediately  after  the  ingestion  of  food, 
the  second  two  or  three  hours  later.     The  rapid  secretion 


212  PHYSIOLOGY  OF  ALIMENTATION. 

which  occurs  at  first  is  found  even  when  the  food  never 
really  enters  the  stomach,  as  in  sham  feeding.  Since  this 
secretion  is  associated  with  the  passionate  desire  for  food, 
or  with  the  mental  impressions  produced  by  the  sight, 
smell,  taste,  etc.,  of  the  food,  it  is  termed  the  "psychic" 
element  in  gastric  secretion.  The  channel  over  which  the 
mental  stimulation  reaches  the  stomach  and  excites  the  lat- 
ter to  secretory  activity  is  represented  by  the  vagus  nerves. 
When  these  are  cut  the  initial  rise  in  gastric  secretion  does  not 
occur.  The  second  great  rise  in  the  curve  of  gastric  secretion 
following  an  ordinary  meal  nevertheless  occurs.  In  what 
way  is  this  second  rise  brought  about? 

The  observations  of  Edkins  1  give  us  an  answer  to  this 
question.  Familiar  with  the  experiments  of  Bayliss  and 
Starling  on  pancreatic  secretin,2  Edkins  cast  about  to  find 
a  gastric  secretin.  His  experiments  show  that  under  the  in- 
fluence of  certain  digestion  products  the  mucosa  of  the  pyloric 
end  of  the  stomach  produces,  during  the  period  of  digestion,  a  sub- 
stance—gastric secretin — which  is  absorbed  into  the  blood  and 
which  excites  the  gastric  glands  to  increased  secretion.  To 
prove  this  Edkins  prepared  extracts  of  the  mucous  membrane 
of  the  pyloric  end  of  the  stomach  by  rubbing  this  up  in  a 
mortar  with  5  percent  dextrin  solutions,  or  solutions  of 
various  sugars  and  peptones.  If  repeated  small  doses  of 
this  extract  are  injected  into  the  circulation  of  a  dog  which 
has  had  its  stomach  filled  with  a  physiological  salt  solution, 
it  is  found  at  the  end  of  an  hour  that  the  salt  solution  con- 
tains both  hydrochloric  acid  and  acid  proteinase.  A  secretion 
of  gastric  juice  is  therefore  excited  by  these  extracts.  It 
can  be  shown  in  control  experiments  in  which  dextrin,  pep- 
tone, etc.,  are  injected  in  pure  solution  into  the  circulation 
that  no  hydrochloric  acid  or  acid-proteinase  can  be  found 
in  the  physiological  salt  solution  recovered  from  the  stomach. 

1  Edkins:  Journal  of  Physiology,  1906,  XXXIV,  p.  133;  Starling: 
Lancet,  1905,  CLXIX,  p.  501. 

2  See  p.  227. 


THE  REGULATION  OF  GASTRIC  SECRETION.       213 

We  may  conclude,  therefore,  thai  l he  increased  .secretion  of 
gastric  juice,  brought  about  through  the  injection  of  extracts 
of  the  mucosa  of  the  pyloric  end  of  the  stomach,  is  due  to  the 
injection  of  some  substance  which  is  produced  in  this  region 
of  the  stomach  under  the  influence  of  certain  of  the  products 
of  gastric  digestion.  This  substance  is  called  gastric  secre- 
tin. The  mucous  membrane  of  the  fundus  of  the  stomach 
does  not  contain  this  substance.  As  to  the  nature  of  gastric 
secretin  but  little  can  be  said.  It  does  not  seem  to  belong  to 
the  class  of  ferments,  for  it  is  not  destroyed  by  boiling.  In 
this  regard  it  is  similar  to  pancreatic  secretin. 

If  now,  in  the  light  of  the  experimental  facts  which  have  been 
cited  above,  we  try  to  explain  the  progress  of  normal  gastric 
digestion  the  following  may  be  said :  The  initial  secretory 
period,  which  is  noted  after  an  ordinary  meal  eaten  in  the 
ordinary  way  and  with  desire,  is  explained  by  the  psychic 
effect  of  eating.  This  psychic  effect  lasts  for  three  or  four 
hours.  The  digestion  periods  following  this  are  independent 
of  the  central  nervous  system  and  are  governed  by  chemical 
agents.  In  the  case  of  meat  we  find  a  reason  for  the  continued 
secretion  of  gastric  juice  after  the  initial  psychic  period  in  the 
chemical  constitution  of  the  food  itself.  It  contains  sub- 
stances which,  acting  on  the  mucosa  of  the  pylorus,  cause 
the  elaboration  of  gastric  secretin.  The  same  holds  true  for 
predigested  foods — that  is,  foods  containing  digestion  products 
which  act  in  a  similar  way  upon  the  pyloric  mucosa.  In  the 
case  of  the  remaining  substances,  such  as  bread  .white  of  egg, 
etc.,  we  can  say  that  under  normal  circumstances  the  psychic 
juice  starts  their  digestion,  and  in  this  process  chemical 
substances  are  formed  which  bring  about  an  elaboration  of 
secretin,  and  this  keeps  up  the  gastric  flow  after  the  psychic 
element  has  come  to  rest.  This  idea  is  supported  by  the  fact 
that  the  products  of  digestion  formed  in  the  stomach  of  one 
dog  act  as  excitants  of  gastric  secretion  when  introduced 
into  the  stomach  of  another.  The  clinical  application  which 
may  be  made  of  these  experimental  facts  is  too  evident  to 


214  *       PHYSIOLOGY  OF  ALIMENTATION. 

need  much  comment.  The  experiments  indicate  very  clearly 
that  lack  of  appetite  means  lack  of  gastric  juice,  which,  in 
turn,  is  synonymous  with  faulty  gastric  digestion.  We  see 
also  the  usefulness  of  predigested  foods  in  certain  pathologi- 
cal conditions  of  the  stomach  and  the  rational  basis  for  the 
use  of  soups,  meat  extracts,  etc.,  which,  though  they  have 
no  food  value  in  themselves,  are  useful  remedial  agents,  since 
they  cause  a  secretion  of  gastric  juice  which  may  be  utilized 
in  digesting  otherwise  indigestible  constituents  of  a  mixed 
meal. 


CHAPTER  XII. 
THE  REGULATION  OF  THE  PANCREATIC  SECRETION. 

i.  Pancreatic  Fistulas.— For  the  study  of  the  quantitative 
and  qualitative  variations  in  the  secretion  of  the  pancreas 
under  different  physiological  conditions  various  experimental 
procedures  have  been  adopted  from  time  to  time.  The  earlier 
observers  contented  themselves  with  isolating  and  dissecting 
out  the  pancreatic  duct,  inserting  a  cannula  into  it,  and  col- 
lecting the  juice  which  flowed  from  it.  It  was  soon  found, 
however,  that  the  aneesthetic,  surgical  shock,  etc.,  so  affected 
the  activity  of  the  gland  as  to  stop  its  secretion  altogether, 
or  at  the  best  allow  the  flow  of  only  a  small  amount,  and  that 
not  very  active  pancreatic  juice. 

In  endeavoring  to  overcome  the  objections  against  such  a 
"temporary"  fistula  of  the  pancreas,  Claude  Bernard  and 
Ludwig  attempted  to  produce  a  "permanent"  one  which 
should  be  free  from  the  immediate  effects  of  an  operation. 
The  former  observer  tied  a  glass  cannula  into  the  secretory 
duct  of  the  pancreas  and  brought  it  out  through  the  abdom- 
inal wall;  the  latter  used  a  lead  wire  to  keep  the  duct  patent. 
The  improved  technique  did,  in  fact,  yield  better  results  than 
the  older  methods,  but  in  the  course  of  five  to  ten  days  the 
cannula  or  wire  sloughed  out,  and  further  experimentation 
was  interfered  with  through  infection  of  the  operation  wound 
and  pancreas. 

In  1879  Pawlow1  and  a  year  later  Heidexhain2  described 

1  Pawlow:  The  Work  of  (he  Digestive  Glands.  Translated  by 
Thompson,  London,  L902,  p.  5. 

2  IIeidknhain:  Hermann's  Ilandbuch  der  Physiologie,  Bd.  V,  p.  177. 

215 


216  PHYSIOLOGY  OF  ALIMENTATION. 

a  surgical  procedure  for  the  production  of  a  "permanent" 
pancreatic  fistula  which  has  stood  the  test  of  time,  and  upon 
which  our  modern  knowledge  of  the  activity  of  the  pancreas 
is  largely  based.  Pawlow's  method  is  as  follows:  An  oval 
piece  containing  the  orifice  of  the  pancreatic  duct  is  cut  out  of 
the  duodenum,  and  the  opening  in  the  intestine  is  closed  by  a 
row  of  sutures.  The  isolated  piece  of  intestine  is  then  carried 
up  into  the  wound  in  the  abdominal  wall  and  sutured  there 
with  the  mucous  membrane  directed  outward.  At  the  end 
of  two  weeks  the  animals  may  be  used  for  study.  When  the 
wound  has  healed,  it  shows  a  roundish  elevation  of  the  mucous 
membrane,  in  the  centre  of  which  the  cleft-like  orifice  of  the 
pancreatic  duct  is  clearly  visible.  By  supporting  the  animal 
in  a  suitable  frame  the  pancreatic  juice  may  now  be  collected 
directly  into  a  graduated  cylinder  as  it  drops  from  the  duct, 
or  if  the  juice  tends  to  spread  over  the  abdominal  wall  a  funnel 
may  be  strapped  over  the  opening  of  the  duct.  If  only  care 
be  taken  to  keep  the  fistulous  opening  clean,  to  avoid  macera- 
tion of  the  skin  by  allowing  the  animal  to  lie  in  sand  or  saw- 
dust which  absorbs  the  pancreatic  juice,  and  to  supply  the 
animal  with  proper  food,  the  dog  operated  upon  in  the  way 
indicated  may  be  kept  for  months  and  even  years  in  a  healthy 
condition. 

More  recently  the  operation  of  Pawlow  and  Heidenhain 
has  been  much  improved  by  Fodera  *  who  succeeded  in  caus- 
ing a  T-shaped  metallic  cannula  to  heal  into  the  pancreatic  duct. 
In  this  way  the  pancreatic  juice  may  be  collected  either  ex- 
ternally or,  by  closing  the  outer  opening,  be  diverted  into 
the  lumen  of  the  intestine.  Thus  the  deleterious  effects  of 
the  constant  loss  of  pancreatic  juice,  necessary  in  Pawlow 
and  Heidenhain's  operation,  is  prevented  during  those  periods 
when  the  animal  is  not  being  used  for  experimental  purposes. 

2.  The  Effect  of  Diet  on  Pancreatic  Secretion. — In  a  dog 
in  which  a  pancreatic  fistula  has  been  created  by  either  the 

1  Fodera:  Moleschott's  Untersuchungen  zur  Naturlehre d.  Menschen 
und  d.  Tiere,  1896,  XVI. 


HEGULATIO.X  OF  Till.    PANCREATIC  SECRETION.     217 

method  of  I'  .\\\  low  or  lo  »i>  ki<  a,  as  described  above,  the  quanti- 
tative and  qualitative  variations  in  the  pancreatic  juice  under 
various  conditions  of  diet,  etc.,  can  be  followed  with  great 
exactness.  As  was  found  to  be  true  in  the  caseof  the  stomach, 
the  secretion  of  pancreatic  juice  is  intimately  connected  with 
the  taking  of  food.  The  pancreatic  secretion,  which,  during 
fasting,  amounts  to  only  two  or  three  cubic  centimeters  in 
twenty-four  hours,  is  increased  to  many  times  that  amount 
as  soon  as  food  is  taken.  The  secretion  from  the  pancreas  is 
poured  out  gradually,  though  different  amounts  cuter  the  in- 
testine in  each  unit  of  time.  The  following  experiment  of 
Walther  l  illustrates  this  point. 

Rate  of  Pancreatic  Secretion  after   Feeding  600  c.c.  Milk. 

Hour  after  feeding.  Quantity  of  juice  in  c.c. 

1 

2 
3 
4 
5 

These  values  are  expressed  graphically  in  Fig.  26. 

Not  only  does  the  quantity  of  pancreatic  juice  secreted 
from  hour  to  hour  vary  but  also  the  quality.  In  the  follow- 
ing table  are  indicated  the  hourly  variations  in  the  digestive 
1  lower  of  pancreatic  juice  after  a  meal  of  600  c.c.  milk.  The 
digestive  power  of  the  fat-splitting  ferment  is  expressed  in 
terms  of  cubic  centimeters  of  a  standard  barium  hydrate 
solution,  required  to  neutralize,  the  acid  formed  in  a  given 
length  of  time,  when  the  specimen  of  pancreatic  juice  is  al- 
lowed to  act  on  a  fat.  The  activity  of  t  he  proteolyl  ic  ferment 
is  determined  by  Mett's  method.  That  of  the  amylolytic 
ferment  is  determined  by  an  analogous  method,  in  which 
colored  starch  paste  is  digested  out  of  capillary  tubes. 
In  the  case  of  the  proteolytic  and  amylolytic  ferments,  the 

1  Walther:  Pawlow's  Work  ol  the  Digestive  Glands,  translated 
by  Thompson,  London,  1902,  p.  22. 


Exp.  o. 

Exp.  6. 

8.75 

8 .  25 

7.5 

6.0 

22.5 

23.0 

9.0 

6.25 

2.0 

1.5 

218 


PHYSIOLOGY  OF  ALIMENTATION. 


activity  is  expressed  in  number  of  centimeters  of  egg-albumin 
or  starch  digested  out  of  the  tubes  in  the  unit  of  time.  As 
has  already  been  pointed  out,  this  method  is  not  free  from 


HOURS 

24 

1 

2 

3 

4 

5 

1 

2 

3 

4 

5 

I 

22 

, 

I 

I 

20 

18 

o 

ol6 

z 

UJ  14 
O 

\ 

1 

1 

o 

fcio 

1- 

2    8 
o 

j 

\ 

\ 

\ 

/ 

"s 

j 

\ 

/ 

6 

/ 

\ 

/ 

\ 

/ 

\ 

/ 

\ 

4 

j 

1 

\ 

/ 

\ 

/ 

\ 

1 

\ 

8 

/ 

\ 

\ 

/ 

\ 

0 

/ 

1 

Fig.  26.     Curve  of  secretion  of  pancreatic  juice  after  feeding  600  c.c. 

milk.     Two  experiments. 

(Copied  from  Pawlow:   Work  of  the  Digestive  Glands.      Trans,  by 

Thompson,  London,  1902,  p.  24.) 

objection.  The  values  obtained  in  different  experiments 
agree  so  well  with  each  other;  however,  that  the  results  must 
be  looked  upon  as  correct,  at  least  in  the  main. 

Hourly  Variation  op  Digestive   Power  of   Pancreatic  Juice 
after  a  Meal  of  600  c.c.  Milk. 


[our. 

Lipolytic  ferment. 

Amylolytic 

ferment. 

Proteolyti 

3  ferment. 

Exp.  a.          Exp.  6. 

Exp.  a. 

Exp.  b. 

Exp.  a. 

Exp.  6. 

1 

14.0            14.0 

5.1 

5.0 

5.8 

5.5 

2 

20.0            13.0 

5.0 

4.7 

5.9 

5.5 

3 

7.0             5.2 

2.4 

2.4 

4.3 

4.1 

4 

6.0             7.0 

3.3 

3.4 

4.5 

4.4 

These  values  are  expressed  in  curves  in  Fig.  27. 


REGULATION  OF   THE  PANCREATIC  SECRETION.     219 


The  cause  of  these  variations  in  the  digestive  power  of  the 
pancreatic  juice  is  not  yet  explained.     A  strong  digestive 


Hours 


1 

1 

4 

> 

t    (i  (1 

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o|4.0 

£     2.0 

i- 

a      0 

20.0 

18. 

16. 

14. 
d 
u 

2  12. 

>- 

S  10. 

< 

u 

o 

a. 

3  G. 
4. 


1        1 


t 

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5  s  2.0 

5     o 



V 

\^, 

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^^ 

^\^ 

L_ 

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V 

t  z 

JZ 

3 

Fig.  27. — Fermentative  activity  of  hourly  portions  of  pancreatic  juice 

after  a  meal  ot  600  c.c.  milk. 

(Copied   from   Pawlow:    Work  of  the  Digestive  Glands.     Trans,  by 

Thompson   London,  1902,  p.  30.) 

power  may  be  found  when  much  juice  is  being  secreted  by 
the  gland  as  well  as  when  the  flow  is  scanty.     The  variations 


220 


PHYSIOLOGY  OF  ALIMENTATION. 


are  probably  associated  with  the  progressive  changes  which 
the  food  undergoes  during  digestion,  but  just  how  they  are 
connected  is  not  yet  known. 

The  variation,  both  in  quality  and  quantity,  which  the  pan- 
creatic juice  suffers  when  different  diets  are  fed  is  indicated  in 
the  following  table.  By  strength  of  juice  is  meant  the  square 
of  the  number  of  millimeters  of  egg-albumin  or  starch  dis- 
solved out  of  the  capillary  tubes,  or  the  square  of  the  num- 
ber of  cubic  centimeters  of  standard  barium-hydrate  solution 
used  to  neutralize  the  acid  formed  from  the  digested  fat. 
By  the  total  quantity  of  ferment  units  is  meant  the  product  of 
the  strength  of  the  juice  multiplied  by  the  quantity  of  the 
juice  in  cubic  centimeters.  The  amounts  of  food  chosen 
represent  equivalents  of  nitrogen  (Walther)  . 


Quan- 
tity of 
juice 
in  c.c. 

Proteolytic 
ferment. 

Amylolytie 
ferment. 

Lipolytic 
ferment. 

Diet. 

Strength 

of 

juice. 

Total 
quan- 
tity ot 
fer- 
ment 
units. 

Strength 

of 

juice. 

Total 
quan- 
tity 
of  fer- 
ment 
units. 

Strength 

of 

juice. 

Total 
quan- 
tity ot 
fer- 
ment 
units. 

Milk,  600  c.c.  . . 
Bread,  250  gms. 
Meat,  100  gms.. 

48 
151 
144 

22.6 
13.1 
10.6 

1085 
1978 
1502 

9 
10.6 
4.5 

432 
1601 

648 

90.3 

5.3 

25.0 

4334 

800 

3600 

In  discussing  the  gastric  secretion  and  its  variations  under 
the  influence  of  different  diets,  it  was  pointed  out  that  not 
only  the  quantity  but  also  the  digestive  power  of  the  juice 
differs  with  different  kinds  of  food.  The  above  table  shows 
that  for  the  pancreatic  juice  it  is  still  more  strikingly  true 
that  each  kind  of  food  has  its  own  particular  kind  of  juice. 
Each  sort  of  food  determines  the  secretion  of  a  definite  amount 
of  pancreatic  juice.  But  still  more  remarkable  is  the  variation 
in  the  amount  of  the  different  ferments  poured  out  upon  the 
foods.  The  juice  poured  out  upon  bread  is  exceedingly  poor 
in  lipolytic  ferment,  while  that  poured  out  upon  milk  is  very 


REGULATION   OF   THE  PAXCREAT1C  SECRETION.     221 

rich.  The  juice  poured  out  upon  meat  occupies  ;ui  inter- 
mediate position  in  this  regard.  The  largest  amylolytic 
activity  is  found  in  the  juice  poured  out  on  bread,  less  in  the 
juice  poured  out  on  milk,  and  still  less  in  that  poured  out 
upon  meat.  It  is  self-evident  that  so  far  as  the  fat-  and  starch- 
splitting  ferments  are  concerned  the  properties  of  the  pan- 
creatic juice  correspond  to  the  requirements  of  the  food.  A 
diet  rich  in  starch  receives  a  juice  rich  in  amylolytic  fer- 
ment, one  rich  in  fat  a  juice  containing  much  lipolytic  fer- 
ment. This  is  shown,  as  indicated  in  the  above  table,  not 
only  by  the  strength  of  juice  poured  out  upon  these  different 
foods  but  also  by  the  absolute  quantities  secreted  by  the 
gland. 

The  behavior  of  the  proteolytic  ferment  seems  at  first  to 
differ  from  that  of  the  amylolytic  and  lipolytic.  In  dis- 
cussing gastric  secretion  it  was  shown  that  the  weakest  juice 
was  poured  out  on  milk.  In  the  case  of  the  pancreas,  how- 
ever, the  strongest  proteolytic  juice  is  poured  out  upon  this 
food,  while  a  weaker  one  is  poured  out  upon  bread  and  a  still 
weaker  one  upon  meat.  When,  however,  the  quantity  of 
juice  poured  out  upon  these  different  foods  is  taken  into  con- 
sideration we  arrive  at  conclusions  similar  to  those  found  to 
hold  for  gastric  secretion.  As  indicated  in  the  above  table, 
when  equivalent  quantities  of  protein  are  fed  in  the  form  of 
bread,  meat,  and  milk,  the  total  quantity  of  ferment  units 
poured  out  upon  these  foods  stands  as  1978:1502:1085.  In 
other  words,  vegetable  protein  demands  from  the  pancreas, 
as  well  as  from  the  stomach,  the  largest  number  of  ferment 
units,  while  milk  demands  the  least.  The  difference  between 
the  secretion  of  the  stomach  and  the  pancreas  is,  therefore, 
limited  to  the  fact  that  the  former  pours  out  its  ferment  in  a 
very  concentrated  form  upon  bread,  while  the  latter  pours 
it  out  in  a  more  dilute  solution.1 

1  SccPawlow:  Work  of  the  Digestive  Glands.  Translated  by  Thomp- 
son ,  London, 1902,  p. 39. 


222  PHYSIOLOGY  OF  ALIMENTATION. 

3.  The  Relation  of  the  Nervous  System  to  Pancreatic 
Secretion. — The  secretion  of  juice  by  the  pancreas  is  in- 
fluenced by  the  vagus  nerve  in  much  the  same  way  as  the 
secretion  from  the  stomach.  In  this  chapter  of  physiology 
also,  Pawlow  and  his  coworkers  have  done  most  within  recent 
years  to  advance  the  state  of  our  knowledge.  The  following 
experiment  shows  unequivocally  that  the  vagus  nerve  con- 
tains fibres  which  influence  the  secretion  of  the  pancreatic 
juice.  A  dog  in  which  a  permanent  pancreatic  fistula  has 
been  made  after  the  fashion  described  above  is  employed.  The 
vagus  nerve  is  divided  in  the  neck  on  one  side,  the  peripheral 
end  is  laid  bare,  and  after  having  a  ligature  passed  around 
it,  is  preserved  under  the  skin.  On  the  fourth  day  after 
division  the  severed  nerve  is  carefully  pulled  out  of  the 
wound  without  hurting  the  dog  in  any  way.  No  juice  flows 
from  the  pancreatic  fistula.  But  one  or  two  minutes  after 
the  peripheral  end  of  the  vagus  is  stimulated  by  an  induc- 
tion current  a  drop  of  juice  appears  at  the  orifice  of  the 
pancreatic  duct,  which  is  soon  followed  by  another  and 
another  in  rapid  succession.  If  the  induction  current  is 
interrupted  the  pancreatic  juice  continues  to  flow  for  four 
or  five  minutes  and  then  ceases.  If  now  the  stimulation  be 
renewed  juice  appears  a  second  time,  and  so  on. 

The  reason  why  the  older  observers  never  obtained  a  flow 
of  pancreatic  juice  when  they  stimulated  the  vagus  is  due  to 
the  fact  that  in  their  experiments  performed  at  one  sitting 
peripheral  stimuli  iuitiated  by  anaesthetic,  pain  due  to  opera- 
tion, etc.,  acted  upon  the  pancreas  and  produced  a  reflex 
inhibition.  That  such  sensory  stimuli  exert  an  inhibitory  ef- 
fect upon  the  pancreatic  gland  has  been  shown  by  Bernstein, 
Pawlow,  and  others.  Circulatory  disturbances  also  inter- 
fere with  pancreatic  activity.  In  the  experiment  described 
above  such  peripheral  stimuli  are  carefully  avoided,  first 
by  utilizing  an  animal  which  has  recovered  from  the  effects 
of  anaesthetic  and  operation,  and  secondly  by  stimulating 
the  vagus  at  a  time  when  its  cardiac  fibres  have  degenerated 


REGULATION  OF  THE  PANCREATIC  SECRETION.     22.1 

to  such  an  extent  that  stimulation  no  longer  affects  the 
heart.  At  this  time  the  fibres  influencing  the  pancreatic 
secretion  are,  however,  still  active. 

But  the  influence  of  (lie  vagus  nerve  can  also  be  demon- 
strated in  an  experiment  performed  at  a  single  sitting.  Special 
precautions  must  be  taken,  however,  to  prevent  the  inhibition 
of  the  gland  either  through  nervous  reflexes  or  through  the 
circulation.  To  do  this  a  dog  has  his  spinal  cord  divided 
just  below  the  medulla  in  order  to  shut  out  all  peripheral 
stimuli  which  might  inhibit  the  activity  of  the  pancreas. 
After  this  has  been  done  and  artificial  respiration  started, 
the  thorax  is  opened  and  the  vagus  divided  below  the  heart. 
If  now  a  cannula  is  inserted  into  the  pancreatic  duct  a  secre- 
tion of  pancreatic  juice  is  noticed  whenever  the  peripheral 
end  of  the  cut  vagus  is  stimulated.  By  thus  exciting  the 
vagus  in  the  thorax  its  influence  on  the  heart  is  avoided. 

The  experiments  of  Popielski  x  indicate  that  the  vagus 
nerve  contains  fibres  which  not  only  augment  the  secretion 
of  the  pancreas  but  also  such  as  inhibit  it.  If  during  the 
acute  experiment  described  above  a  solution  of  hydrochloric 
acid  is  poured  into  the  duodenum  a  vigorous  secretion  of 
pancreatic  juice  is  called  forth  which  continues  for  a  long 
time.  If  now  the  vagus  nerve  be  stimulated  the  secretion  is 
markedly  diminished  in  amount,  often  stopped  entirely. 

The  pancreas  is  influenced  also  by  the  sympathetic  nerve, 
as  shown  by  the  experiments  of  Kudrewetzky.2  This  nerve 
apparently  carries  two  kinds  of  fibres  to  the  gland — first, 
vaso-constrictor,  and  secondly,  such  as  influence  the  secretory 
activity  of  this  organ.  If  the  sympathetic  is  stimulated  in 
the  ordinary  way  by  electric  induction  shocks  a  slighl  in- 
crease in  secretion  is  observed,  which  lasts,  however,  only  a 
few  seconds;  then  it  ceases  entirely  even  if  the  electrical 
Stimulation  is  continued.      This   is  due   to   the   fact    that    the 


1  Popiei.ski-  c.ni  rail. 1.  f.  Physiol.,  1896,  X,  p.  105. 

■  Kudrewetzky;  Archiv  t.  (Anat.  u.)  Physiol.,  1894,  p.  s::. 


224  PHYSIOLOGY  OF  ALIMENTATION. 

vasoconstrictor  effects  completely  mask  the  secretory. 
The  two  can  be  separated  by  mechanical  stimulation  of  the 
sympathetic.  When  this  is  done  stimulation  always  leads 
to  an  increased  secretion  from  the  gland,  for,  as  is  well  known, 
vaso-constrictor  nerve  fibres  are  not  readily  excited  by 
mechanical  means.  The  two  can  also  be  separated  by  stim- 
ulating the  sympathetic  several  days  after  it  has  been  divided. 
The  vaso-constrictor  fibres  are  the  first  to  degenerate,  so  that 
only  those  influencing  the  secretory  activity  of  the  gland  are 
left  to  exhibit  their  characteristic  effects. 

4.  The  Normal  Excitants  of  the  Pancreas. — It  has  been 
shown  above  that  during  a  period  of  digestive  inactivity  the 
pancreas  secretes  no  juice;  that  after  feeding,  a  large  amount 
of  pancreatic  juice  is  secreted.  What  determines  this  secre- 
tion? The  relation  of  the  various  inorganic  constituents 
of  the  food  to  the  pancreatic  flow  has  been  studied  by 
Becker  1  and  Dolinski.2 

Acids  of  all  kinds  act  as  powerful  excitants  of  the  pan- 
creatic secretion.  If  250  c.c.  of  a  0.5  percent  hydrochloric  acid 
solution,  for  example,  are  introduced  by  means  of  a  catheter 
into  the  stomach  of  a  dog  possessing  a  permanent  pancreatic 
fistula,  the  inactive  pancreas  begins  to  secrete  within  two  or 
three  minutes.  Within  ten  minutes  the  pancreatic  flow 
reaches  its  maximum  and  within  the  first  hour  some  80  c.c. 
of  juice  may  be  collected.  The  rate  of  secretion  steadily 
falls,  so  that  towards  the  end  of  the  second  hour  only  about 
15  c.c.  can  be  collected  before  the  outflow  ceases  entirely. 
If,  instead  of  the  hydrochloric  acid  solution,  an  equal  amount 
of  water  is  injected  into  the  stomach  little  or  no  pancreatic 
juice  is  obtained,  which  shows  that  it  is  the  acid  which  is 
active.  That  at  the  end  of  such  an  experimental  period  the 
pancreas  is  not  exhausted  can  be  readily  proved  by  injecting 

1  Becker:  Archives  des  Sciences  Biologiques,  II,  p.  433.  Pawlow's 
Work  of  the  Digestive  Glands.  Translated  by  Thompson,  London, 
1902,  p. 113. 

2  Dolinski:  Arch,  des  Sci.  Biolog.,  Ill,  p.  399. 


REGULATION  OF    THE  PANCREATIC  SECRETION.     225 

the  hydrochloric  acid  a  second  time,  when  figures  practically 
the  same  as  those  given  above  can  again  be  obtained.  Phos- 
phoric, citric,  lactic,  and  acetic  ackl  behave  in  a  way  similar 
to  hydrochloric.     Carbonic  ackl  also  belongs  in  this  group. 

Sodium  chloride  in  solution  seems  to  be  without  effect 
upon  the  pancreas,  and  alkaline  solutions,  such  as  calcium 
hydroxide,  sodium  bicarbonate,  and  alkaline  mineral  waters, 
have  a  distinctly  inhibitory  effect  upon  its  secretion. 

After  what  has  been  said  it  is  not  strange  that  gastric  juice 
acts  as  a  chemical  excitant  of  the  pancreas,  and  to  the  same 
degree  as  a  hydrochloric  acid  solution  of  the  same  concentra- 
tion. When  the  gastric  juice  of  the  acid  food  passing  out 
of  the  stomach  is  neutralized  the  effect  of  the  latter  in  calling 
forth  a  pancreatic  secretion  disappears.  In  what  way  the 
acid  is  effective  in  acting  upon  the  pancreas  will  be  discussed 
later  when  we  speak  of  secretin. 

In  spite  of  the  fact  that  starch  is  one  of  the  constituents  of 
the  food  upon  which  the  pancreatic  juice  acts,  this  carbohy- 
drate, whether  boiled  or  unboiled,  and  at  any  concentration, 
affects  the  quantity  of  juice  poured  out  by  the  pancreas  no 
more  than  an  equal  amount  of  water.  A  qualitative  change 
in  its  composition  is,  however,  rendered  probable  by  the  ex- 
periments of  Walther,  who  found  that  a  dog  when  fed  on 
bread  secretes  a  pancreatic  juice  richer  in  amylolytic  ferment 
than  when  fed  with  meat. 

Fat  seems  to  be  an  excitant  of  the  pancreas.  Dolinski 
and  Damaskin  l  found  that  after  introducing  oil  into  the 
stomachs  of  dogs  a  flow  of  pancreatic  juice  always  ensued. 

Do  we  have  a  psychic  secretion  of  pancreatic  juice  similar 
to  the  psychic  secretion  of  gastric  juice?  This  question  can- 
not yet  be  looked  upon  as  definitely  settled.  Kuwschinski  2 
showed  in  1888  that  tempting  a  hungry  dog  with  Food  led 

1  Pawlow:  Work  of  the  Digestive  Glands.  Translated  by  Thompson, 
London, 1902,  p. 121. 

;  Kuwschinski:  Paw  'low's  Work  of  the  Digestive  Glands,  Trans- 
lated by  Thompson,  London,  1902,  p.  121. 


226  PHYSIOLOGY  OF  ALIMENTATION. 

to  a  free  secretion  of  pancreatic  juice.  This  does  not  prove, 
however,  that  the  pancreas  can  be  directly  excited  by  this 
means,  for  to  tempt  a  hungry  dog  is  to  excite  a  gastric  secre- 
tion, and  the  acid  flow  produced  in  this  way  might  readily  be 
the  real  excitant  of  the  pancreatic  flow.  Two  facts,  however, 
point  strongly  in  favor  of  the  existence  of  a  psychic  secretion 
of  pancreatic  juice.  First,  tempting  a  dog  with  food  or 
sham  feeding  will  cause  a  quiescent  pancreas  to  become 
active  even  when  a  gastric  fistula  allows  the  escape  of  the 
gastric  juice  from  the  stomach  as  soon  as  formed ;  secondly, 
the  latent  period  marking  the  beginning  of  secretion  from  the 
stomach  and  the  pancreas  is  different  in  the  two  cases.  An 
acid  flow  begins  from  the  stomach  five  to  ten  minutes  after 
the  beginning  of  sham  feeding.  The  pancreas  begins  to 
secrete  after  two  to  three  minutes.  If  the  acid  and  not  a 
true  psychic  element  were  responsible  for  the  secretion  of 
pancreatic  juice  the  pancreas  should  not  become  active  until 
after  the  gastric  flow  has  commenced. 

Water  also  acts  as  an  excitant  of  the  pancreas.  When 
150  c.c.  of  water  are  introduced  unnoticed  into  the  stomach 
of  a  dog  the  pancreas  begins  to  secrete,  or  augments  its  flow 
two  or  three  minutes  after  the  water  has  entered  the  stomach. 
If  the  experiment  is  properly  performed  this  amount  of  water 
does  not  excite  a  flow  of  gastric  juice,  so  that  a  secretion  of 
pancreatic  juice  secondary  to  a  secretion  of  gastric  juice  is 
out  of  the  question  here. 

Meat  extracts,  which  were  found  above  to  be  such  good  ex- 
citants of  the  gastric  glands,  are  no  more  effective  in  the  case 
of  the  pancreas  than  an  equal  amount  of  water. 

What  has  been  said  in  this  section  regarding  the  influence 
of  acids,  food,  etc.,  on  the  qualitative  and  quantitative  com- 
position of  the  pancreatic  juice  in  the  dog  seems  to  hold 
without  modification  for  the  human  being.  As  evidence  in 
this  direction  we  may  cite  the  experiments  of  Glaessner1  on 

1  Glaessner;  Zeitschrift  fur  physiologische  Chemie,  1904,  XL,  p.  46f 


REGULATION  OF   THE  PANCREATIC  SECRETION.     227 

his  patient  with  a  fistula  of  the  pancreatic  duel .  (  Ilaessnek 
fmmd  thai  the  amount  of  juice  secreted  in  the  unit  of  time 
was  greatly  increased  soon  after  his  patient  took  food. 
Whereas  under  ordinary  circumstances  10  to  15  c.c.  (lowed 
from  the  fistula  per  hour,  38  c.c.  were  obtained  in  the  first 
hour  alter  a  meal,  34  c.c.  in  the  second,  and  46  c.c.  in  the 
fourth.  From  this  hour  on  the  flow  steadily  decreased 
until  at  the  end  of  the  eighth  it  had  fallen  to  its  original  level. 
It  is  evident,  therefore,  that  the  curve  representing  the  rate 
of  secretion  in  the  human  being  is  similar  to  that  which  has 
been  described  for  dogs. 

The  amount  of  lipolytic,  amylolytic,  and  proteolytic  fer- 
ment in  the  unit  volume  of  pancreatic,  juice  Glaessner  also 
found  to  vary  with  the  taking  of  food.  Between  meals  this 
was  least,  while  the  slow  rise  which  began  during  the  first 
or  second  hour  after  eating  was  found  to  attain  its  maximum 
about  the  fourth,  when  it  fell  once  more  in  the  following  four 
1  lours  to  its  original  level.  The  alkalinity  of  the  juice  was 
also  found  to  increase  after  the  taking  of  food.  While  with 
phenolphthalein  as  indicator  1  c.c.  of  decinormal  acid  was  re- 
quired to  neutralize  10  c.c.  of  pancreatic  juice  between  meals, 
it  required  5  c.c.  of  the  acid  to  neutralize  the  same  amount  of 
juice  obtained  during  the  fourth  hour  after  a  meal. 

The  presence  of  an  acid  in  the  duodenum  seems  to  increase 
the  pancreatic  flow  in  a  human  being  just  as  in  a  dog. 
Glaessner  found  that  the  introduction  of  several  hundred 
cubic  centimeters  of  a  weak  hydrochloric  acid  into  the 
stomach  of  his  patient  was  followed  almost  immediately  by  an 
increased  pancreatic  flow  which  attained  its  maximum  by  the 
end  of  the  first  hour,  and  fell  to  the  original  level  once  more 
by  the  end  of  the  second,  as  in  the  case  of  the  dog. 

5.  Pancreatic  Secretin. — In  discussing  the  effect  of  acids 
upon  the  pancreal  ic  flow,  do  mention  was  made  of  the  mechan- 
ism by  which  this  most  powerful  excitant  of  the  gland  accom- 
plishes its  results.  Pawlow  believed  that  the  gland  was 
excited  through  a  nervous  reflex,  initiated  by  the  effect  of 


228  PHYSIOLOGY  OF  ALIMENTATION. 

the  acid  upon  the  mucous  membrane  of  the  duodenum. 
That  this  explanation  is  incorrect  is  indicated  by  the  experi- 
ments of  Popielski,  Wertheimer,  and  Lepage,  who  found 
that  the  introduction  of  acid  solutions  into  the  stomach  or  duo- 
denum still  excited  the  gland  to  secretion,  when  all  the  nerves 
supplying  the  pancreas  and  duodenum  had  been  cut.  These 
authors,  nevertheless,  clung  to  the  idea  of  a  nervous  excita- 
tion of  the  gland,  at  least  in  part.  What  had  been  rendered 
probable  through  the  experiments  of  Popielski,  Wertheimer, 
and  Lepage  was  made  still  more  evident  by  the  researches 
of  Bayliss  and  Starling,  who  found  that  it  is  possible  to 
isolate  the  pancreas  from  the  duodenum,  to  divide  all  the 
nerves  going  to  a  loop  of  the  small  intestine,  and  nevertheless 
get  a  copious  pancreatic  secretion  soon  after  an  acid  is  injected 
into  this  loop. 

How,  then,  does  the  acid  act?  The  experiments  of  Bay- 
liss and  Starling  *  have  shown  that  the  connection  between 
intestine  and  pancreas  is  really  only  a  chemical  one.  The 
introduction  of  an  acid  into  the  duodenum  or  upper  part 
of  the  small  intestine  brings  about  the  production  of  a  chemi- 
cal substance  in  the  mucous  membrane  which  is  called  secretin. 
Since  there  are  other  secretins,  it  is  well  to  call  the  one  under 
consideration  here  pancreatic  secretin.  As  the  pancreatic 
secretin  is  formed  it  is  rapidly  absorbed  into  the  blood,  with 
which  it  travels  to  the  pancreas,  and  excites  this  organ  to 
secretory  activity. 

Pancreatic  secretin  may  be  obtained  from  the  upper  part 
of  the  intestine  of  any  of  the  vertebrates.  It  is  best  pre- 
pared by  scraping  off  the  mucous  membrane  of  the  upper 
two  feet  of  the  small  intestine,  treating  this  in  a  mortar  with 
sand  and  0.4  percent  hydrochloric  acid,  and  then  boiling  the 
mixture.  After  neutralization  with  caustic  soda  the  whole 
is  filtered.  The  clear  liquid  which  passes  through  the  filter 
contains  the  secretin.      In  order  to  obtain  the  secretin  in  a 

1  Bayliss  and  Starling:  Proceedings  of  the  Royal  Society,  1904, 
LXXIV,p.310;    Starling:  Lancet,  1905,  CLX1X,  pp.  339,  423,  501, 


REGULATION  OF   THE  PANCREATIC  SECRET ION      229 

still  purer  state,  the  filtrate  may  be  treated  with  absolute 
alcohol  and  ether,  which  precipitates  certain  impurities  but 
allows  the  secretin  to  remain  in  solution.  Secretin  is  there- 
fore a  substance  which  is  unaltered  by  boiling  and  is  soluble 
in  alcohol.  It  can  moreover  be  shown  that  it  is  diffusible. 
It  is  not  necessary  that  the  mucous  membra.ne  from  which 
the  pancreatic  secretin  is  to  be  obtained  should  be  living. 
It  can  be  obtained  just  as  well  from  an  intestine  which  has 
been  killed  by  boiling.  Pancreatic  secretin  has,  therefore, 
none  of  the  ordinary  characteristics  of  a  ferment,  and  recent 
experiments  seem  to  indicate  that  it  belongs  to  the  class  of 
the  peptones.  It  is  possible,  therefore,  that  secretin  repre- 
sents nothing  but  a  product  of  proteolytic  activity. 

A  few  cubic  centimeters  of  the  secretin-containing  filtrate 
obtained  as  described  above  when  injected  into  the  veins  of 
an  animal  call  forth  a  plentiful  secretion  of  clear  pancreatic 
juice,  which  may  be  collected  by  means  of  a  cannula  placed 
in  the  pancreatic  duct.  The  pancreatic  secretin  obtained 
from  one  animal  is  not  specific  for  that  class  alone,  but  will 
when  injected  into  the  veins  of  any  other  vertebrate  call 
forth  a  copious  pancreatic  flow.  It  is  wrell  to  add  that  the 
pancreatic  juice  obtained  after  the  injection  of  secretin  is  to 
all  appearances  identical  with  that  obtained  after  an  ordinary 
meal. 

Bayliss  and  Starling's  findings  alter  somewhat  our  con- 
ception of  the  events  which  follow  each  other  in  the  intestinal 
canal.  A  consideration  of  the  facts  which  have  been  out- 
lined above  makes  us  imagine  the  changes  which  occur  here 
to  be  somewhat  as  follows:  The  acid  gastric  contents  enter 
the  duodenum  and  bring  about  the  formation  of  pancreatic 
secretin.  This  is  absorbed  into  the  circulation  and,  passing 
with  the  blood-current  through  the  pancreas,  causes  a  secre- 
tion of  pancreatic  juice.  Since  the  pancreatic  juice  is  able  to 
neutralize  free  acids,  it  will  decrease  little  by  little  the  acidity 
of  the  gastric  contents  which  have  come  into  the  duodenum. 
Little  by  little  also  will  the  rate  of  production  of  secretin  be 


230  PHYSIOLOGY  OF  ALIMENTATION. 

decreased.  But  not  until  all  the  acid  in  the  duodenum  has 
been  neutralized  will  the  production  of  pancreatic  secretin, 
and,  in  consequence,  the  pancreatic  flow,  cease  entirely. 

This  chemical  interaction  between  the  stomach,  duodenum, 
and  pancreas  is  further  aided  by  the  rhythmic  opening  and 
closing  of  the  pyloric  sphincter,  which  has  already  been  de- 
scribed.1 The  presence  of  free  hydrochloric  acid  in  the 
stomach  causes  the  pyloric  sphincter  to  relax  and  some  of 
the  gastric  contents  to  pass  into  the  duodenum.  As  soon 
as  the  acid  reaches  this  part  of  the  intestinal  canal,  however, 
the  sphincter  is  closed  reflexly,  and  remains  closed  until  the 
duodenal  contents  have  become  neutralized  by  being  mixed 
with  pancreatic  juice.  As  soon  as  this  neutralization  has 
been  accomplished,  the  pylorus  relaxes  a  second  time  and  a 
fresh  portion  of  the  gastric  contents  enters  the  duodenum. 
This  in  its  turn  calls  forth  a  production  of  pancreatic  secretin, 
a  secretion  of  pancreatic  juice,  and  the  cycle  is  repeated. 

6.  Significance  of  the  Physiology  of  the  Gastric  and  Pan- 
creatic Secretions. — The  advances  made  in  our  knowledge  of 
gastric  and  pancreatic  activity  have  done  much  to  give  us  an 
experimental  basis  for  what  has  hitherto  been  empirical  in 
medical  practice  and  have  at  the  same  time  pointed  out  the 
direction  which  medicine  must  take  in  combating  certain 
affections  of  the  alimentary  tract.  The  experimental  results 
detailed  above  show  most  clearly  the  physiological  impor- 
tance of  the  appetite.  Appetite  is  synonymous  with  a  copious 
secretion  of  gastric  juice,  and  the  necessity  of  this  secretion 
for  a  proper  and  rapid  digestion  of  proteins  and  the  evil 
effect  of  its  absence  are  manifest  nowhere  more  clearly  than 
in  those  disorders  which  are  associated  with  a  deficient  secre- 
tion from  the  stomach.  We  recognize,  in  consequence,  the 
importance  of  catering  to  the  appetite  in  health,  in  order  to 
maintain  gastric  digestion  at  its  best,  and  the  urgency  of 
restoring  this  physiological  sense  in  those  diseases  in  which 

1  See  p.  16. 


REGULATIOX  OF   THE  PANCREATIC  SECRETION.     231 

it  is  absent.  As  the  pancreatic  secretion  is  probably  in- 
fluenced by  appetite  in  the  same  way  as  the-  stomachy  v.  • 
an  additional  reason  for  recognizing  its  medical  importance. 
The  influence  of  the  appetite  upon  the  secretion  of  the  gastric 
juice  contributes  also  to  our  understanding  of  the  beneficent 
effects  which  follow  the  feeding  of  a  patient  with  a  "weak" 
stomach  at  frequent  intervals  and  only  small  amounts  at  a 
time.  Under  these  circumstances  the  appetite  juice,  rich  in 
ferments,  recurs  several  times  and  digestion  is  furthered  in 
consequence. 

We  are  also  in  a  position  to  understand  now  the  good  effects 
of  condiments  and  bitters.  Pharmacologists  have  looked  in 
vain  for  a  direct  secretory  effect  of  these  substances  upon 
the  stomach  and  pancreas,  Every-day  observation,  however, 
seems  to  support  indisputably  the  fact  that  these  substances 
increase  the  appetite.  If  this  be  true,  we  have  arrived  at  an 
explanation  of  the  good  effects  following  their  moderate  use, 
for  to  increase  appetite  is  to  increase  gastric  and  pancreatic 
secretion.1  We  can  recognize  also  the  relation  which  appetite 
and  gastric  secretion  bear  to  each  other.  Quite  contrary 
to  the  generally  accepted  idea  that  the  presence  of  gastric 
juice  in  the  stomach  is  the  cause  of  appetite,  we  must  say  that 
gastric  secretion  is  its  consequence. 

It  is  necessary  to  revise  our  ideas  of  the  usefulness  of  meat 
soups,  meat  extracts,  meat  juices,  etc.  Few  medical  men  to- 
day are  not  acquainted  with  the  valuelessness  of  the  first  two 
from  a  nutritive  standpoint.  But  since  they  excite  a  secre- 
tion of  gastric  juice,  even  in  the  absence  of  appetite,  they  are 
eminently  useful,  for  they  can  in  this  way  be  employed  to 
bring  about  the  digestion  of  food  which  is  introduced  into 
the  stomach  subsequently.  Because  of  this  fact  soups  ful- 
fil a  good  function  when  employed  at  an  ordinary  meal,  for 
they  help  to  maintain  a  secretion  of  digestive  juice  which  has 
been  inaugurated  by  the  appetite. 

1  SeePAWLOw:  Work  of  the  Digestive  Glands.  Translate!  1  by  Thomp- 
son, London,  1902,  p.  13S  et  scq. 


232  PHYSIOLOGY  OF  ALIMENTATION. 

Milk  and  water  are  also  independent  excitants  of  the  gastric 
secretion,.  We  find  in  this  another  reason  for  the  use  of  water 
with  meals.  Milk  has  from  the  earliest  times  been  considered 
an  easily  digested  food  for  children  and  invalids.  Not  only 
does  this  fluid  cause  a  secretion  of  gastric  juice,  but,  as  has 
been  shown  above,  a  weaker  gastric  juice  and  a  smaller 
quantity  of  pancreatic  juice  are  poured  out  on  milk  than  on 
an  equivalent  amount  of  nitrogen  contained  in  any  other 
food.  The  work  performed  by  these  digestive  glands  is 
therefore  less,  and  the  saving  of  energy,  in  consequence,  is 
greater  than  when  meat  or  bread,  for  example,  is  fed.  The 
amount  of  work  which  the  organism  does  in  order  to  assimi- 
late a  certain  amount  of  nutriment  must  always  be  sub- 
tracted from  the  energy  value  of  the  food  itself.  This  is  not 
ordinarily  considered  in  determining  the  value  of  various 
foods.  We  have  seen  above,  however,  that  equivalent 
weights  of  nitrogen  in  the  proteins  of  meat,  bread,  and 
milk  cost  the  organism  different  amounts  of  glandulai 
energy. 

Fat  inhibits  the  secretion  of  gastric  juice.  We  find  in  this 
the  explanation  of  the  fact  that  its  presence  in  a  mixed  meal 
impedes  the  rate  of  digestion,  and  hence  is  contraindicated  in 
cases  of  feeble  digestion,  while  it  works  excellently  in  cases 
of  hyperacidity  and  hypersecretion.  The  alkalies  and  alka- 
line salts  belong  in  this  group  of  substances  which  inhibit  the 
secretions  of  the  gastric  mucosa  and  the  pancreas. 

We  have  learned  from  experiments  detailed  above  the 
uselessness  of  mechanical  stimulation  of  the  gastric  mucosa 
in  bringing  about  a  secretion  of  gastric  juice.  Neither 
mechanical  stimulation  through  coarse  food  or  by  means 
of  special  apparatus,  such  as  an  inflatable  balloon,  can  there- 
fore be  looked  upon  as  rational  treatment  for  those  gastric 
disorders  which  are  characterized  by  deficient  secretion  of 
juice.  Care  must  be  taken  not  to  confound  this  statement 
with  the  relation  between  mechanical  stimulation  and  the 
motor  functions  of  the  stomach. 


REGULATION  OF  THE  PAXCREATIC  SECRETION.     233 

A  defective  secretion  of  gastric  juice,  be  its  cause  what  it 
may,  is  of  medical  importance  from  other  points  of  view 
than  that  it  interferes  with  the  proper  digestion  of  proteins. 
A  lack  of  hydrochloric  acid  in  the  stomach  allows  the  develop- 
ment here  of  a  large  number  and  variety  of  bacteria  which 
in  its  presence  is  impossible.  The  development  of  these 
bacteria  is  associated  with  fermentative  changes  in  the 
stomach  contents,  which  assume  clinical  importance  in  pro- 
portion to  their  character  and  amount.  Lack  of  free  hydro- 
chloric acid  in  the  stomach  delays  the  opening  of  the  pyloric 
sphincter,  which  leads  to  retention  of  the  food  in  the  stomach 
for  longer  periods  of  time  than  normally.  In  this  way  also 
bacterial  fermentation  is  allowed  to  become  more  effective. 

When  ultimately  the  stomach  contents  pass  into  the  small 
intestine,  they  flood  this  portion  of  the  alimentary  tract  with 
bacteria  and,  as  already  pointed  out,  the  bactericidal  activity 
of  the  small  intestine  is  by  no  means  limitless.  The  fermenta- 
tive changes  in  the  food  initiated  in  the  stomach  may  in  con- 
sequence continue  in  the  intestine,  with  effects  upon  the 
organism  as  a  whole  (due  in  part  to  absorption  of  the  bacterial 
products  formed,  in  part  to  a  lack  of  properly  digested  foods) 
which  are  sometimes  unimportant,  sometimes  serious. 

A  deficient  amount  of  gastric  juice  leads  to  yet  other  dis- 
turbances in  the  organism.  We  are  slowly  beginning  to 
recognize  the  intimate  connection  which  exists  between 
different  organs  in  the  body  and  how  the  proper  behavior 
of  one  is  dependent  upon  that  of  another.  This  relation 
between  organs  exists  also  between  different  portions  of  the 
alimentary  tract.  It  might  be  thought  at  first  that  from 
the  standpoint  of  digestion  alone  a  deficient  amount  of  gastric 
juice  is  without  consequence,  for  the  pancreas  contains  a 
proteolytic  ferment  which  is  able  to  split  proteins  even  more 
readily  than  the  acid-protoinase  of  the  stomach.  Matters 
are  not  so  simple,  however.  It  was  seen  above  that  the 
presence  of  acids  in  the  duodenum  brings  about  a  secretion 
of  pancreatic   juice.      If  now   the   gastric   secretion  is  de- 


234  PHYSIOLOGY  OF  ALIMENTATION. 

ficient,  it  means  a  lack  of  acid  in  the  duodenum,  and  this 
in  turn  means  a  deficient  secretion  of  pancreatic  juice. 

7.  On  the  "  Adaptation  "  of  the  Digestive  Glands  to  the 
Character  of  the  Food. — The  opinion  that  the  secretions 
of  the  various  digestive  glands  "adapt"  themselves  to  the 
character  of  the  food  consumed  by  the  individual,  that,  in 
other  words,  each  diet  calls  forth  a  particular  kind  of  diges- 
tive secretion,  has  been  expressed  from  time  to  time  by  various 
authors.  With  all  of  them,  however,  this  opinion  has  rested 
more  upon  philosophical  speculations  than  upon  experimental 
facts. 

The  first  to  attempt  to  give  experimental  foundation  to  such 
an  idea  was  Pawlow,  and  with  him  Chigin  and  Walther. 
But  the  experiments  which  these  investigators  have  detailed 
in  support  of  their  belief,  and  which  have  been  touched  upon 
in  the  preceding  pages,  have  been  so  energetically  attacked 
by  others  that,  at  the  best,  they  can  be  looked  upon  as  by 
no  means  convincing. 

With  all  the  more  pleasure,  therefore,  can  we  proceed  to  a 
discussion  of  the  experiments  of  Weinland,1  which  indicate 
without  question  that  one  digestive  gland  at  least,  the  pan- 
creas, can  and  does  "adapt"  itself  to  a  particular  diet. 
Weinland 's  experiments  show  that  the  pancreas  and  pre- 
sumably, therefore,  the  pancreatic  juice  of  the  adult  dog, 
which  normally  contain  little  or  no  lactase,  come  to  con- 
tain this  enzyme  in  large  amounts  if  the  dog  is  fed  milk- 
sugar,  or  a  diet  containing  milk-sugar,  such  as  milk.  This 
means  that  the  pancreas  and  pancreatic  juice,  which  in  the 
adult  dog  normally  contain  little  or  no  ferment  which  can  act 
upon  lactose  and  split  this  into  .galactose  and  dextrose,  de- 
velop this  sugar-splitting  ferment  in  response  to  certain  diets. 

What  has  been  said  can  be  best  illustrated  by  introducing 
one  of  Weinland 's  experiments.  An  adult  dog  was  kept  on 
an  abundant  diet,  but  free  from  milk-sugar,  for  five  days; 

1  Weinland:  Zeitschr.  f.  Biol.,  1899,  XXXVIII,  p.  16;  ibid.,  1899, 
XXXVIII,  p.  607;  ibid.,  1900,  XL,  p„  386. 


REGULATION  OF    THE   PANCREATIC  SECRETION.     235 

he  was  killed  and  the  pancreas  removed  immediately,  an 
extract  made  of  it  and  its  power  of  acting  upon  milk-sugar 
(lactase  content)  determined.  The  extracl  was  found  to 
have  practically  no  effect  upon  milk-sugar,  indicating,  there- 
fore, (hal  it  contained  little  or  no  ferment  capable  oi  acting 
on  lactose.  A  second,  also  advli  dog  received  for  15  days  a 
diet  similar  to  that  given  the  first  dog, only  :!()  gms.  of  milk- 
sugar  were  added  to  the  daily  food  ration.  When  at  the 
end  of  this  time  the  dog  was  killed,  the  pancreas  removed 
and  treated  as  that  of  the  first  dog,  it  was  found  that  the 
'pancreatic  extract  split  milk-sugar  most  energetically  into  galac- 
tose and  dextrose,  43  percent  of  the  added  lactose  being 
split  within  twenty-four  hours.  It  is  self-evident,  therefore, 
that  under  the  influence  of  milk-sugar  feeding  the  pancreas 
can  develop  a  ferment  (lactase)  which  has  the  power  of  split- 
ting milk-sugar  and  which  is  entirely  absent  (or  present  in 
only  very  small  amounts)  in  the  pancreas  of  an  adult  dog 
not  so  fed. 

The  percent  of  sugar  split  as  given  above  is  by  no  means 
the  highest  that  Weinland  ever  attained.  In  three  other 
experiments  in  which  the  dogs  were  fed  ordinary  milk  instead 
of  pure  milk-sugar,  the  pancreatic  extracts  were  able  to  split 
respectively  54  percent,  73  percent,  and  75  percent  of  the 
lactose  added  to  them.  When  it  is  pointed  out  that  the 
pancreas  obtained  from  dogs  of  a  corresponding  age,  but  not 
fed  on  milk-sugar,  possess  practically  no  milk-sugar-splitting 
activity  it  is  self -apparent  how  striking  is  this  "adaptation'' 
of  the  pancreas  to  the  character  of  the  diel . 

It  is  of  physiological  interest  that  the  quantitative  variation 
in  the  amount  of  lactase  found  not  only  in  the  pancreas  but 
also  in  the  small  intestine  is  intimately  connected  with  the 
age  of  the  individual,  or,  as  we  can  say  now,  with  those 
periods  of  life  in  which  milk-sugar  furnishes  a  pari  of  the 
food  consumed  by  the  animal.  Apparently  all  sucklings 
(including  Hie  new-born  child)  have  lactase  present  in  the 
pancreatic   juice   and    the   intestinal   juice.     This   has   been 


236  PHYSIOLOGY  OF  ALIMENTATION. 

proven  true  for  all  mammals  examined.  In  adult  life, 
however,  the  lactase  of  the  pancreas  disappears  very  largely, 
at  times  entirely,  and  the  lactase  of  the  intestinal  mucosa  and 
its  secretion  decreases  much  in  amount  (and  in  some  animals 
disappears  entirely)  unless  milk-sugar  continues  to  serve  as 
an  article  of  food  for  the  adult  animal. 

We  have  yet  to  discuss  the  mechanism  of  this  adaptation. 
A  direct  effect  of  the  milk-sugar  upon  the  pancreas  from  the 
lumen  of  the  intestine  is  practically  impossible,  for  the  pan- 
creas is  connected  with  the  gut  by  only  a  slender  excretory 
duct,  through  which,  moreover,  during  the  periods  of  diges- 
tion an  uninterrupted  stream  of  juice  pours.  It  might  be 
thought  that  when  an  excessive  amount  of  milk-sugar  is  fed, 
some  passes  over  into  the  circulation,  for  we  can  discover 
milk-sugar  in  the  urine;  and  this  absorbed  sugar  might  be 
thought  to  act  directly  upon  the  pancreas.  That  this  idea 
is  not  correct  follows  from  the  fact  that  the  intravenous 
or  subcutaneous  injection  of  milk-sugar  is  not  followed  by 
the  appearance  in  the  pancreas  of  an  increased  amount  of 
lactase.  Neither  does  a  subcutaneous  or  intravenous  injec- 
tion of  one  of  the  products  of  milk-sugar  digestion,  such  as 
galactose,  accomplish  this  result.  In  order  that  this  may 
occur  the  milk-sugar  must  come  in  contact  with  the  mucosa  of 
the  intestine. 

We  are  indebted  to  Vernon  1  for  a  further  analysis  of  the 
problem.  This  author,  who  entirely  confirms  the  experimental 
findings  of  Weinland,  has  shown  that  through  contact  of  the 
milk-sugar  with  the  intestinal  mucosa  a  substance  is  produced 
which  is  absorbed  into  the  blood  and  which  when  it  is  carried 
to  the  pancreas  brings  about  in  this  organ  an  increased  pro- 
duction of  lactase.  This  phenomenon  belongs,  therefore,  in 
the  same  group  with  those  which  we  discussed  under  the 
heading  of  the  secretins.2  We  have  here  another  example  of 
the  chemical  connection  which  exists  between  different  organs. 

1  Vernon:  Journal  of  Physiology,  1905.        2  See  pp.  211  and  227. 


CHAPTER  XIII. 

THE  REGULATION   OF  THE   BILIARY  AND  INTESTINAL 
SECRETIONS— THE  FUNCTIONS  OF  THE  BILE. 

i.  The  Secretion  of  Bile. — In  discussing  the  question  of 
the  secretion  of  bile  we  must  distinguish  between  the  forma- 
tion of  the  bile  in  the  liver,  together  with  its  collection  in 
the  gall-bladder,  and  the  flow  of  the  bile  into  the  intestinal 
canal.  The  two  processes  go  on  independently  of  each  other, 
and  the  older  experiments  made  by  producing  a  fistula  of  the 
gall-bladder  give  us  an  insight  only  into  the  first  of  these 
questions.  What  determines  the  flow  of  bile  into  the  intestinal 
canal? 

This  question  has  recently  been  investigated  by  Bruno  and 
Kladnizki,1  who  have  .succeeded  in  turning  the  orifice  of  the 
gall-duct  outwards  in  such  a  way  that  the  bile  flows  out 
upon  the  skin.  This  they  accomplish  by  cutting  out  of  the 
intestine  the  orifice  of  the  duct  with  its  surrounding  mucous 
membrane  and  suturing  the  latter  to  the  serous  coat  of  the 
duodenum.  The  entire  loop  of  intestine  is  then  sewed  into 
the  abdominal  wound. 

Contrary  to  the  older  observations  made  on  gall-bladder 
fistula?  it  has  been  found  that  the  bile  does  not  flow  into  the 
intestine  all  the  time.  The  secretion  of  bile  is  intimately 
connected  with  taking  food  and  does  not  begin  until  a  definite 
time  has  elapsed  after  partaking  of  a  meal.  The  length 
of  this  latent  period  differs  with  the  different  kinds  of  food. 
The  secretion  continues  as  long  as  the  period  of  digestion, 

1  Buuno  and  Kladnizki:  Pawlow's  Work  of  (he  Digestive  Cdands. 
Translated  by  Thompson.  London,  1902,  p.  155.  Bruno:  Review 
in  Jahresber.  d.  Thierchemic    XXVII,  p.   111. 

237 


238  PHYSIOLOGY  OF  ALIMENTATION. 

but  not  at  an  even  rate,  fluctuating  in  quantity  with  varia- 
tions in  the  nature  of  the  food. 

When  different  food  substances  are  fed  separately  to  a  dog 
operated  upon  as  indicated  above,  it  is  found  that  neither 
water,  acids,  raw  white  of  egg,  nor  boiled  starch  as  a  thick  or 
a  thin  paste  causes  a  flow  of  bile.  Fat,  however,  and  to  a 
less  extent  extractives  of  meat,  and  the  digestion  products 
of  white  of  egg  set  up  a  free  discharge  of  the  secretion.  The 
bile,  therefore,  is  not  unlike  the  gastric  or  pancreatic  juice, 
which  has  each  its  specific  excitants. 

How  now  do  the  various  substances  which  bring  about  a 
secretion  of  bile  into  the  intestine  do  this?  The  explana- 
tion which  has  been  and  is  given  ordinarily  is  that  the  bile 
flows  in  consequence  of  a  nervous  reflex  which  is  initiated 
through  the  action  of  certain  constituents  of  the  intestinal 
contents  upon  the  mucous  membrane  of  the  duodenum.  It 
is  much  more  probable,  however,  that  the  connection  between 
duodenum  and  liver  is  of  a  chemical  character.  This  is  shown 
by  the  experiments  of  Bayliss  and  Starling,  who  find  that 
pancreatic  secretin  not  only  augments  the  flow  of  pancreatic 
juice  but  also  the  discharge  of  bile  into  the  intestine.  It  is 
an  interesting  fact  that  the  pancreas  and  liver  should  have 
such  a  common  excitant,  for  as  will  be  shown  immediately 
the  bile  augments  in  a  most  marked  way  the  digestive  prop- 
erties of  the  pancreatic  juice. 

2.  The  physiological  importance  of  the  bile  is  shown  very 
clearly  in  the  classical  observation  of  Claude  Bernard  and 
the  more  modern  one  of  Dastre.1  Claude  Bernard  noticed 
that  in  rabbits,  in  which  the  opening  of  the  pancreatic  duct 
into  the  intestine  lies  some  30  cm.  below  that  of  the  bile- 
duct,  the  absorption  of  fat  after  a  fatty  meal  does  not  begin 
until  the  food  has  passed  the  pancreatic  duct,  for  while  the 
lymph  leaving  the  intestine  below  this  point  is  milky  in  ap- 
pearance that  above  it  is  clear.     This  shows  that  the  bile 

1  Dastre:  Arch,  de  pliys.  norm,  et  path.,  1890,  XXII,  p.  315. 


BILIARY   AND  INTESTINAL  SECRETIONS.  239 

alone  is  unable  to  bring  about  an  absorption  of  fat.    Dastre's 

experiments  consisted  in  producing  artificially  in  dogs  the 
reverse  of  the  above  conditions.  After  ligating  the  bile-dud 
he  established  a  fistulous  opening  between  the  gall-bladder 
and  the  middle  of  the  small  intestine.  In  spite  of  the  fact 
that  the  pancreatic  juice  entered  the  duodenum  as  usual, 
no  fat  was  absorbed  from  the  entire  upper  half  of  the  small 
intestine.  Not  until  the  biliary  fistula  was  passed  did  the 
lacteals  show  a  milky  appearance  to  indicate  fat  absorption. 
This  shows  how  important  is  the  function  of  the  bile  for  the 
rapid  and  proper  absorption  of  fats,  and  indicates  clearly 
that  physiological  ends  are  best  served  when  pancreatic  juice 
and  bile  act  together  upon  fat. 

The  important  role  of  the  bile  in  the  digestion  of  fats  can 
also  be  shown  very  clearry  in  experiments  carried  out  in  glass. 
Heidenhain,  Williams,  and  Martin  have  all  shown  that  the 
presence  of  bile  in  a  reaction  mixture  of  fat  and  pancreatic 
lipase  markedly  increases  the  velocity  of  the  formation  of 
fatty  acid  and  alcohol.  Especially  commendable  are  the 
recent  experiments  of  Rachford,  Bruno,  and  Glaessner, 
carried  out  with  purified  ferments  instead  of  ordinary  extracts 
of  the  pancreas,  or  the  pure  pancreatic  and  biliary  secretions 
themselves.  Glaessner's  *  results  are  given  in  the  following 
table  and  deal  with  human  pancreatic  juice.  It  is  interesting 
to  note  that  what  Schepowalnikow  observed  in  dogs  is  true 
here  also,  namely,  the  simultaneous  presence  of  both  bile 
and  intestinal  juice  favors  the  lipolytic  activity  of  the  pan- 
creatic juice  more  than  that  of  either  one  by  itself.  The 
last  column  indicates  the  percent  of  fatty  acid  formed  in 
twenty-four  hours. 

Fatty 
acid. 

100  c.c.  olive-oil +  20  c.c.  pancreatic  juice =_'_", 

100  c.c.  olive-oil  +  20  c.c.  pancreatic  juice  +  10  c.c.  bile =30% 

100  c.c.  olive-oil  +  20  c.c.  pancreatic  juice+  10  c.c.  intestinal  juice     35'  , 
100  c.c.  olive-oil  +  20  c.c.  pancreal  ic  juice+  L0  c.c.  bile  :  10  c.c.  in- 
testinal juice =    in1, 

1  Glaessner:  Zeitschr.  I.  physiol.  Chem.,  XL,  p.  170. 


240  PHYSIOLOGY   OF  ALIMENTATION. 

A  long-accepted  explanation  of  the  role  of  bile  in  hastening 
fat  digestion  has  been  sought  in  its  power  of  favoring  the 
emulsification  of  fats.  Through  emulsification  of  the  fat  the 
amount  of  surface  exposed  to  the  action  of  lipase  is  greatly 
increased.  Experiments  carried  out  by  Hewlett  x  indicate 
that  bile  acts  in  yet  another  and  even  more  direct  way  than 
this  in  favoring  the  activity  of  the  ferment.  These  experi- 
ments show  at  the  same  time  which  constituent  of  the  bile 
it  is  that  favors  the  fat-splitting  activity  of  the  pancreatic 
juice,  for  bile  is  a  mixture  of  a  number  of  chemical  entities. 

If,  instead  of  the  ordinary  very  sparingly  soluble  fats,  the 
soluble  triacetin  is  used,  so  that  the  question  of  emulsification 
plays  no  part  whatsoever,  it  is  found  that  bile  still  markedly 
hastens  the  action  of  pancreatic  juice  upon  this  substance. 
In  one  experiment,  for  example,  pure  pancreatic  juice  ob- 
tained from  a  dog  by  secretin  and  atropin  injections  pro- 
duced in  one  hour  at  20°  C.  enough  acid  to  require  0.5  c.c. 
1/20  normal  alkali  solution  to  neutralize  it,  and  in  twenty- 
four  hours  12.6  c.c.  In  another  tube  which  contained  the 
same  amount  of  pancreatic  juice  and  triacetin,  but  in  addi- 
tion a  small  amount  of  bile,  the  acidity  produced  in  one  hour 
amounted  to  13.0  c.c,  in  twenty-four  hours  to  18.6  c.c.  of 
a  1/20  normal  alkali  solution.  That  the  acceleration  of  the 
decomposition  in  the  later  hours  of  the  experiment  should 
be  less  than  in  the  earlier  is  readily  explained  by  the  fact 
that  the  reaction  is  approaching  an  equilibrium. 

If  now  an  attempt  is  made  to  discover  which  constituent 
of  the  bile  it  is  that  favors  in  this  way  the  decomposition  of 
triacetin  under  the  influence  of  pancreatic  juice,  it  is  found, 
first  of  all,  that  boiling  the  bile  does  not  destroy  this  property. 
It  is  therefore  probable  that  we  are  not  dealing  with  the 
action  of  any  enzyme  contained  in  the  bile.  Hewlett  has 
further  shown  that  this  property  resides  neither  in  the  choles- 
terin  nor  in  the  bile  pigments,  nor  in  variations  in  the  reac- 

1  Hewlett:  Johns  Hopkins  Hospital  Bulletin,  1905,  XVI,  p.  20. 


BILIARY  AND  INTESTINAL  SECRETIONS.  241 

tion  or  in  the  amount  of  calcium  salts  present.  All  the 
accelerating  effects  of  bile  upon  the  lipolytic  activity  of 
pancreatic  juice  can  be  equally  well  produced  by  (lie  ad- 
dition of  lecithin.  This  is  shown  very  well  in  the  follow- 
ing table,  in  which  is  indicated  the  number  of  cubic  cen- 
timeters of  a  1/20  normal  alkali  solution  which  were  required 
to  neutralize  the  acid  formed  in  twenty-four  hours  in  three 
tubes  containing  the  same  amounts  of  pancreatic  juice  and 
triacetin. 

Pancreatic  juice  + triacetin =  4.3  c.c. 

Pancreatic  juice  +  triacetin +  2  c.c.  bile =19.5  c.c. 

Pancreatic  juice  +  triacetin +  2  drops  alcoholic  solution  of 

lecithin =  19 . 9  c.c. 

Commercial  bile  salts  also  accelerate  the  action  of  pan- 
creatic juice  on  triacetin,  but  when  these  salts  are  purified 
they  lose  this  power,  which  seems  to  indicate  that  the  action 
of  the  crude  preparation  is  determined  solely  by  its  con- 
tamination with  lecithin. 

As  to  the  manner  in  which  the  bile  assists  the  lipolytic 
action  of  the  pancreatic  juice,  we  have  as  yet  no  satisfactory 
explanation. 

Bile  also  favors  the  action  of  some  of  the  other  ferments 
contained  in  the  pancreatic  juice.  But  while  bile  may  even 
treble  the  velocity  with  which  fats  are  digested,  it  only  doubles 
the  velocity  with  which  amylase  will  act  on  starch,  or  alkali- 
proteinase  (trypsin)  on  proteins. 

Aside  from  its  action  as  an  aid  to  the  pancreatic  ferments, 
bile  has  yet  other,  though  perhaps  scarcely  as  important, 
functions.  While  a  large  number  of  the  fatty  acids  are  freely 
soluble  in  water,  this  is  not  true  of  the  fatty  acids  derived 
from  most  of  the  fats  (stearin,  palmitin,  olein)  which  consti- 
tute our  food.     Moore,  Rockwood,  and  Pfluger's  1  studies 

1  Moore  and  Rockwood:  Journal  of  Physiology,  1897,  XXI,  p.  58. 
Tfluueh's  numerous  papers  on  fat  are  contained  in  Pfluger's  Archiv, 
Vols.  LXXX  to  LXXXVI  (1900  to  1901). 


242  PHYSIOLOGY  OF  ALIMENTATION. 

are  therefore  of  great  importance,  which  show  that  a  mix- 
ture of  bile  and  sodium  carbonate  is  able  to  dissolve  large 
amounts  of  stearic  and  palmitic  acids.  Bile  is  able  to  keep 
even  the  insoluble  calcium  and  magnesium  soaps  in  solution. 

The  presence  of  bile  in  a  reaction  mixture  of  protein  and 
gastric  juice  retards  the  action  of  the  ferment  greatly.  It 
seems  plausible,  therefore,  that  the  bile  is  of  physiological 
importance  by  interfering  with  the  activity  of  the  gastric 
juice  after  this  escapes  into  the  duodenum  from  the 
stomach. 

To  the  bile  has  also  been  attributed  an  antiseptic  action, 
and  it  has  been  believed  that  through  its  presence  the  de- 
velopment of  bacteria  throughout  the  alimentary  tract  is 
markedly  inhibited.  Careful  study  seems  to  indicate,  how- 
ever, that  this  antiseptic  action  is  only  very  weak,  if  it  is  pres- 
ent at  all.  Bacteria  develop  freely  in  bile  itself  and  culture 
media  containing  bile.  The  increased  putrefaction  of  the 
alimentary  contents,  which  is  observed  in  at  least  some  cases 
of  icterus,  must  therefore  be  attributed  to  other  causes. 
Foremost  among  these  must  stand  the  less  perfect  absorption 
of  the  foodstuffs  whose  presence  in  the  alimentary  tract 
furnishes  a  ready  culture  ground  for  the  various  bacteria 
found  here. 

The  bile  is  believed  to  aid  intestinal  peristalsis.  This 
idea  seems  borne  out  by  clinical  observation,  though  labora- 
tory experiments  in  this  direction  have  brought  no  unequivo- 
cal results.  If  it  is  true  that  a  lack  of  bile  leads  to  a  de- 
creased peristalsis,  we  could  readily  find  in  the  retention  of 
alimentary  contents  from  this  cause  an  additional  reason  for 
the  increased  intestinal  putrefaction  found  in  these  cases. 

We  must,'  in  conclusion,  call  attention  to  a  function  of  the 
bile  which  is  still  questioned  by  some  authors.  According 
to  some  recent  experiments,  it  is  claimed  that  lipase  is  secreted 
in  the  pancreatic  juice  only  in  an  inactive  form,  that  is,  as  a 
proferment  or  zymogen,  and  that  this  inactive  form  is  acti- 
vated through  the  bile.     The  bile  would  therefore  serve  the 


BILIARY   AND   INTESTINAL  SECRETIONS.  243 

same  importanl  function  in  fat  digestion  thai  the  intestinal 
juice  serves  through  the  enterokinase  it  contains  in  protein 
digesl  ion. 

3.  Regulation  of  the  Intestinal  Secretion. — In  order  to 
obtain  a  collection  of  pure  intestinal  juice  use  is  made  of 
Thiry's  classical  fistula.,  or  Thiry's  fistula  as  modified  by 
Vella.  An  opening  is  made  in  the  abdominal  wall  of  an 
animal,  and  a  suitable  loop  of  intestine  is  pulled  out.  Two 
transverse  cuts  separate  any  desired  length  of  the  intestine 
from  the  main  portion  of  the  tube,  the  continuity  of  which  is 
restored  by  an  end-to-end  anastomosis.  The  separated 
loop  of  intestine  is  then  closed  at  one  end  by  a  purse-string 
suture,  while  the  opposite  end  is  sewed  into  the  edges  of  the 
wound.  In  this  way  a  test-tube  shaped  piece  of  the  bowel 
is  separated  from  the  main  body  of  the  gut  (Thiry  fistula), 
or  both  ends  may  be  sewed  into  the  abdominal  wound  when 
we  have  the  so-called  Thiry-Vella  fistula.  The  artificial 
production  of  all  the  most  successful  fistula?  along  the  gastro- 
intestinal tract  is  modelled  after  the  original  Thiry  operation 
on  the  small  intestine. 

In  the  quiescent  state  of  the  animal  practically  no  secre- 
tion can  be  obtained  from  such  an  isolated  loop  of  intestine. 
As  soon  as  food,  such  as  starch  paste,  sugar,  or  peptone,  is 
introduced  into  the  loop  an  increased  secretion  takes  place. 
Apparently,  therefore,  intestinal  juice  is  secreted  under 
ordinary  circumstances  only  by  those  portions  of  the  gut 
with  which  food  is  in  contact,  and  not  throughout  its  entire 
length.  The  presence  of  food  may  cause  a  secretion  either 
through  ils  mechanical  or  chemical  properties.  That  mere 
mechanical  stimulation  may  be  effective  in  causing  a  secre- 
tion of  intestinal  juice  is  proved  by  the  fact  that  the  irritation 
of  a  cannula  in  an  intestinal  fistula,  a  rubber  ball,  etc.,  all 
lead  to  a  secretion  of  juice.  According  to  Pawlow  and  his 
coworkers  the  intestinal  juice  obtained  in  consequence  of 
mechanical  stimulation  alone  differs  from  that  obtained  by 
chemical  means.     The  former  kind  consists  chiefly  of  water 


244  PHYSIOLOGY  OF  ALIMENTATION. 

and  salts  with  but  very  little  or  no  enter okinase.1  When  the 
secretion  is  poured  out  upon  food  the  intestinal  juice  is  rich 
in  enterokinase.  Apparently  much  more  powerful  than  the 
food  itself  in  bringing  about  an  intestinal  secretion  are  the 
pancreatic  ferments  which,  under  ordinary  circumstances, 
accompany  the  food  along  the  intestine.  An  isolated  loop 
which  is  secreting  little  or  no  juice  will  become  active  very 
soon  after  a  few  cubic  centimeters  of  pancreatic  juice  are 
put  into  it.  If  the  pancreatic  juice  is  previously  boiled,  this 
property  is  lost.  Which  of  the  pancreatic  ferments  is  active 
in  this  direction  is  not  yet  known. 

Observers  agree  that  the  normal  enteric  juice  is  a  thin, 
slightly  yellowish  liquid,  ordinarily  said  to  be  alkaline  in 
reaction.  The  fluid  which  collects  in  the  course  of  a  few 
weeks  in  loops  of  intestine  which  are  ligatured  off  from  the 
main  tube  probably  does  not  represent  a  normal  secretion. 
Usually  this  is  more  or  less  gelatinous  and  represents  no 
doubt  the  inspissated  intestinal  juice  plus  the  mucin  and 
other  abnormal  substances  poured  out  by  the  loop  in  conse- 
quence of  the  "catarrh"  which  arises  in  it. 

The  nervous  system  no  doubt  influences  the  secretion 
from  the  small  intestine,  but  in  just  what  way  is  not  known. 
The  statements  made  by  different  observers  contradict  each 
other  in  many  points.  A  secretion  of  fluid  occurs  into  the 
intestine  when  all  the  nerves  passing  to  the  loop  have  been 
severed.  This  so-called  "paralytic  secretion"  contains,  ac- 
cording to  Mendel's  observations,  all  the  ferments  present  in 
the  normal  juice.  A  secretion  of  fluid  into  isolated  loops  of 
intestine  when  entirely  removed  from  the  body  also  occurs. 
All  the  structures  necessary  for  secretion  must  therefore  be 
contained  in  the  wall  of  the  gut,  and  it  would  no  doubt  be 
straining  a  point  should  we  attribute  this  secretion  to  the 
nervous  plexuses  found  in  the  wall  of  the  intestine,  and  not 
solely  to  the  mucous  membrane.  The  fluid  secreted  into 
loops  entirely  removed  from  the  body  is  not  to  be  regarded 

1  See  p.  240. 


BILIARY  A.XD  INTESTINAL  SECRETIONS.  245 

as  normal  intestinal  juice.  For  this  we  need  the  cooperation 
of  the  circulating  blood,  from  which  are  taken  the  substances 
which  cither  directly  or  after  they  have  been  changed  into 
new  chemical  compounds  through  the  activities  of  the  mucous 
membrane  go  to  make  up  the  intestinal  juice. 

Stimulation  of  the  vagus  nerve  in  the  neck  or  below  the 
diaphragm  seems  not  to  affect  the  secretion  of  enteric 
juice.  Removal  of  the  cceliac  or  mesenteric  plexuses  seems 
to  bring  about  an  increased  secretion  similar,  perhaps,  to 
the  ordinary  paralytic  secretion  but  not  so  great  in  amount. 
If  certain  of  the  ganglia  are  left  behind,  the  secretion  may 
not  take  place. 

Attention  has  already  been  called  to  the  fact  that  the 
intestinal  juice  has  not  the  same  chemical  composition  through- 
out its  entire  length.  Special  mention  must  be  made  of  the 
secretion  of  the  duodenum.  In  addition  to  the  glands  of 
Lieberkuhn  found  throughout  the  whole  of  the  small  intes- 
tine the  duodenum  contains  the  glands  of  Brunner.  His- 
tologically these  resemble  the  glands  of  the  stomach.  The 
debate  which  has  long  been  carried  on  as  to  whether  the 
proteolytic  ferment  found  in  the  duodenal  juice  is  acid-  or 
alkali-proteinase,  or  amphoproteinase  can  be  looked  upon  as 
decided  through  Abderhalden's  work.  While  it  is  impossible 
under  certain  circumstances  to  say  whether  we  are  dealing 
with  pepsin  or  trypsin  when  a  fluid  containing  one  or  both 
of  them  is  allowed  to  act  on  fibrin  or  any  other  complex  pro- 
tein, it  is  possible  to  do  this  when  polypeptides  are  used.  Al- 
kali-proteinase will  split  certain  polypeptides  not  affected  by 
acid-proteinase  and  vice  versa.  In  this  way  it  has  been  possi- 
ble to  prove  that  the  proteolytic  powers  of  the  duodenal  juice 
are  due  to  acid-proteinase  (pepsin)  secreted  by  the  glands  of 
Brunner.  As  is  universally  the  case,  the  proteolytic  fer- 
ment of  the  duodenal  juice  is  also  accompanied  by  a  milk- 
curdling  ferment.  As  a  whole,  therefore,  the  duodenal  juice 
is  very  like  gastric  juice,  yet  the  physiological  importance 
cf  (he  latter  when  compared  with  the  former  is  not  great. 


246  PHYSIOLOGY  OF  ALIMENTATION. 

The  secretion  of  the  large  intestine  is  small  in  amount  and 
rich  in  mucin.  It  is  stated  to  be  alkaline  in  reaction,  and  to 
contain  no  ferments  in  sufficient  amount  to  be  of  physiologi- 
cal importance.  The  large  intestine  acts  chiefly  as  an  organ 
of  absorption. 

4.  Enterokinase. — This  is  the  term  given  by  Pawlow  to  a 
substance  discovered  by  Schepowalnikow  in  the  mucous 
membrane  of  the  small  intestine  which  has  the  interesting 
property  of  inaugurating  or  at  least  of  increasing  enormously 
the  proteolytic  power  of  the  pancreatic  juice  as  it  flows  from 
the  gland. 

We  are  probably  correct  in  believing  that  neither  the  pan- 
creas nor  the  pancreatic  juice  obtained  directly  from  the 
pancreatic  duct  contains  any  alkali-pro teinase  (trypsin),  but 
only  a  substance  (the  so-called  proferment  or  zymogen)  which 
can  be  converted  into  this  ferment  through  contact  with 
enterokinase.  Under  physiological  conditions  this  contact 
with  enterokinase  is  established  as  soon  as  the  pancreatic 
juice  flows  over  the  mucous  membrane  of  the  small  intestine, 
the  walls  and  secretions  of  which  contain  this  activating  sub- 
stance. The  amount  of  mucous  membrane  necessary  to 
bring  about  at  least  some  activation  of  the  otherwise  inactive 
pancreatic  juice  is  very  small  according  to  Delezenne  and 
Frouin's  1  experiments.  In  the  ordinary  method  of  making 
a  pancreatic  fistula  according  to  the  method  of  Heidenhain 
and  Pawlow,2  by  cutting  out  a  small  portion  of  the  mucous 
membrane  surrounding  the  pancreatic  duct  and  sewing  this 
into  the  edge  of  the  abdominal  wound,  the  escape  of  the  pan- 
creatic secretion  over  this  bit  of  mucous  membrane  is  sufficient 
to  give  it  well-marked  digestive  properties  for  proteins.  If 
the  escape  of  the  juice  across  the  transplanted  mucous  mem- 
brane is  avoided  by  inserting  a  cannula  into  the  duct  above 

1  Delezenne  and  Frotjin:  Compt.  rend,  de  Soc.  biol.,  1902 
CXXXIV,  p.  1524. 

2  See  p.  215. 


BILIARY  AND  INTESTINAL  SECRETIONS.  247 

it ,  juice  cut  irely  incapable  of  digesting  egg  albumin  is  obtained. 

This  juice  readily  becomes  active  in  this  direction  if  a  .small 
amount  (a  drop  or  two)  of  intestinal  juice  obtained  from 
an  intestinal  fistula  in  another  animal  is  added  to  it. 

As  to  the  nature  of  enterokinase  but  little  is  known  at 
present,  for  the  substance  cannot  be  obtained  in  even  an 
approximately  pure  state.  Since  it  is  readily  destroyed  at 
comparatively  low  temperatures  Pawlow  has  looked  upon  it 
as  a  ferment.  This  conception  of  enterokinase  scarcely  har- 
monizes with  the  observations  that  have  been  made,  which 
indicate  that  a  definite  amount  of  enterokinase-containing 
fluid  can  activate  only  a  limited  amount  of  pancreatic  juice. 
True  ferments,  it  is  well-known,  act  upon  an  infinite  amount 
of  substance  if  only  sufficient  time  is  given. 

The  secretion  of  enterokinase  is  not  to  be  looked  upon  as 
a  function  performed  by  the  small  intestine  at  all  times. 
Enterokinase  appears  and  disappears  from  the  juice  poured 
out  by  the  upper  portions  of  the  small  intestine  in  the  same 
way  as  the  amount  of  bile  poured  into  the  duodenum  is  con- 
trolled by  such  circumstances  at  the  taking  of  food.  In  fact, 
the  secretion  of  enterokinase  is  connected  with  physiological 
processes  going  on  in  the  intestine  in  the  same  way  as  the 
secretion  of  bile.  When  the  small  intestine  is  stimulated 
mechanically  it  secretes  a  juice,  but  it  is  thin  and  watery  and 
contains  practically  no  enterokinase.  As  soon,  however,  as 
a  few  cubic  centimeters  of  pancreatic  juice  are  introduced 
into  the  lumen  of  the  intestine,  the  juice  secreted  becomes 
rich  in  enterokinase.  Boiled  pancreatic  juice  does  not  have 
this  power.  The  secretion  of  the  watery  constituents  and 
of  the  enterokinase  of  the  intestinal  juice  represent,  there- 
fore, different  physiological  processes. 

The  idea  that  pancreatic  juice  obtained  directly  from  the 
pancreatic  duct  has  no  power  to  digest  proteins  contradicts 
the  views  of  a  number  of  observers  who  have  claimed  that 
the  spleen  furnishes  at  the  height  of  digestion  a  substance 
which  is  absorbed  into  the  blood  and  through  its  action  on 


248  PHYSIOLOGY  OF  ALIMENTATION. 

the  pancreas  changes  the  proferment  found  here  into  alkali- 
proteinase.  This  function  of  the  spleen  we  may  no  doubt 
now  say  does  not  exist,  and  may  safely  attribute  the  results 
obtained  by  the  workers  on  the  spleen  to  accidental  bacterial 
contamination  of  the  extracts  with  which  they  worked.  We 
know  now  that  bacteria  can  also  activate  the  proferment 
of  alkali-proteinase,  and  presume  that  they  are  able  to  do  this 
because  of  a  "kinase"  which  they  also  contain. 

Attention  has  several  times  been  called  to  the  physiological 
connection  which  exists  between  different  portions  of  the 
alimentary  tract.  It  may  not  be  amiss  to  do  it  once  more 
at  this  place.  The  bile  and  the  intestinal  juice,  which  so 
markedly  increase  the  activities  of  the  ferments  found  in  the 
pancreatic  secretion  are  poured  into  the  intestine  in  an  ap- 
parently entirely  purposeful  manner.  Bayliss  and  Starling 
have  found  that  pancreatic  secretin,  which  so  markedly  in- 
creases the  discharge  of  pancreatic  juice,  increases  also  the 
flow  of  bile.  If  a  cannula  is  tied  into  the  bile-duct  after 
previous  ligature  of  the  gall-bladder,  the  intravenous  injec- 
tion of  secretin  brings  about  not  only  a  flow  of  pancreatic 
juice  but  also  an  augmented  flow  of  bile.  According  to  De- 
lezenne  pancreatic  secretin  increases  also  a  discharge  of 
intestinal  juice  containing  enterokinase  from  the  upper  por- 
tions of  the  small  intestine.  Through  such  means  the  com- 
bined action  of  pancreatic  juice,  intestinal  juice,  and  bile 
upon  the  food  as  it  escapes  from  the  stomach  is  secured; 
in  other  words,  the  conditions  are  established  which  experi- 
ment has  shown  to  be  the  most  favorable  for  the  rapid 
digestion  (and  absorption)  of  the  various  foodstuffs. 


CHAPTER  XIV. 

THE  ALIMENTARY   TRACT   AS   AN   ABSORPTIVE  SYSTEM. 

i.  The  Problem  of  Absorption. — The  problem  of  the  ab- 
sorption of  foodstuffs  from  the  alimentary  tract  is  the  same 
as  the  problem  of  absorption  in  general.  It  is  self-evident 
that  absorption  and  secretion  are  really  only  different  phases 
of  the  same  thing,  for  in  the  one  case  we  are  asked  to  explain 
why  a  tissue  takes  up  a  certain  chemical  substance,  while 
in  the  other  we  are  called  upon  to  tell  how  a  tissue  rids  itself 
of  this  same  chemical  substance.  In  the  last  anlaysis  we 
have  to  answer  these  questions  for  every  individual  cell,  for 
each  absorbs  certain  substances  and  secretes  others.  Very 
often  one  and  the  same  cell  absorbs  and  secretes  the  same 
substance.  As  will  become  apparent  later  the  intestinal 
epithelium,  for  instance,  absorbs  fat  from  the  lumen  of  the 
gut  and  secretes  it  into  the  lymph  stream.  The  lymph  may 
therefore  be  looked  upon  as  an  absorptive  (fluid)  tissue  which 
in  turn  becomes  a  secretory  tissue  when  the  body  cells  begin 
to  take  the  fat  away  from  it. 

Put  briefly,  therefore,  we  can  say  that  in  considering  the 
problem  of  absorption  we  have  to  answer  the  question,  How 
do  the  various  chemical  substances  pass  from  one  cell  into 
another,  or  from  one  cell  into  a  liquid  (such  as  the  lymph  or 
blood),  or  finally  from  such  a  liquid  into  a  cell?  Under  the 
last  heading  comes,  for  example,  the  passage  of  the  chemical 
substances  contained  in  the  lumen  of  the  alimentary  tract 
into  the  cells  lining  this  tract,  while  the  passage  of  these  same 

249 


250  PHYSIOLOGY  OF  ALIMENTATION. 

substances  into  the  lymph  or  blood  stream  illustrates  the 
second  of  the  above  headings. 

The  natures  of  the  chemical  substances  which  pass  in  this 
way  from  one  cell  to  another  or  from  one  tissue  into  another 
of  necessity  differ  greatly  from  each  other.  Limiting  our- 
selves for  the  moment  simply  to  the  food  ingested  at  an 
ordinary  mixed  meal  we  can  readily  recognize  the  very  large 
number  of  different  chemical  compounds  with  which  we  have 
to  deal.  It  is  possible  to  group  all  of  them  chemically  under 
a  few  headings, — the  proteins,  the  carbohydrates,  the  fats, 
the  salts,  and  water.  As  the  problem  of  absorption  is  a 
physico-chemical  one  we  will  regroup  them  in  a  somewhat 
different  way  as  the  colloids,  the  crystalloids,  and  water. 

Still  more  difficult  is  it  to  say  what  forces  are  active  in 
bringing  about  the  movement  of  these  various  chemical 
substances.  One  of  the  most  readily  intelligible  of  these  is, 
perhaps,  diffusion,  which  is  nothing  but  an  expression  of 
differences  in  osmotic  pressure.  Capillary  forces  must  also 
be  considered  in.  a  discussion  of  the  means  by  which  chemical 
substances  move  from  place  to  place.  Finally  we  can  mention 
the  variable  mechanical  affinity  (Ostwald)  of  colloids  for  water 
and  substances  dissolved  in  the  water.  The  forces  active 
here  are  not  as  yet  clearly  understood.  They  may  be  capil- 
lary in  character  or  connected  with  the  enormous  surface 
presented  by  colloids.  At  any  rate,  modern  investigations 
support  strongly  the  idea  that  an  understanding  of  the  laws 
underlying  the  absorption  of  water  by  colloids  will  do  more 
to  give  us  an  insight  into  the  phenomena  of  absorption  and 
secretion  than  the  laws  of  osmotic  pressure  and  diffusion 
have  ever  done. 

But  the  problem  of  absorption  is  not  stated  when  we  say 
that  we  have  to  explain  the  movement  of  a  large  number  of 
different  chemical  substances  under  the  influence  of  different 
forces.  The  activity  of  these  forces  is  largely  altered  by  the 
fact  that  the  passage  of  the  different  chemical  substances 
from  cell  to  cell,  or  from  liquid  to  cell,  or  from  cell  back  to 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  251 

liquid,  is  modified  by  the  existence  of  differences  in  the  perme- 
ability of  protoplasm,  more  particularly  by  the  existence  of 
cell  membranes  which  arc  sometimes  permeable,  sometimes 
impermeable,  or    again    partially  permeable  to  a  diffusing 

substance.  Not  only  do  different  colls  differ  in  their  perme- 
ability to  certain  chemical  substances,  but  the  same  cell  may 
under  different  conditions  be  at  times  permeable,  at  others 
impermeable,  to  the  same  substance. 

When  we  consider  that  under  ordinary  circumstances  the 
different  chemical  substances,  the  different  forces,  and  the 
different  permeabilities  of  protoplasm  are  all  working  to- 
gether in  making  up  a  picture  of  absorption  as  we  witness  it 
in  a  physiological  experiment  some  idea  may  be  obtained 
of  the  difficulties  which  face  the  investigator  who  attempts 
the  solution  of  the  problem.  Nevertheless  great  strides  have 
been  made  within  recent  years  in  substituting  known  laws  of 
physics  and  chemistry  for  the  vitalistic  explanations  of  the 
older  observers.  In  the  following  paragraphs  are  discussed 
in  brief  the  physical  chemistry  of  the  substances  which  serve 
as  food,  the  forces  active  in  bringing  about  their  absorption, 
and  the  membranes  which  alter  so  markedly  the  independent 
activities  of  the  other  two.  It  is  beyond  the  scope  of  this 
volume  to  enter  more  deeply  than  this  into  the  subject. 

2.  The  Physical  Character  of  the  Foodstuffs.  Colloids 
and  Crystalloids. — From  the  standpoint  of  absorption  the 
chemical  constitution  of  the  foods  which  we  consume  plays 
less  of  a  role  than  their  physical  character.  It  is  for  this 
reason  that  a  regrouping  of  these  substances  into  colloids^, 
crystalloids,  and  water  has  been  suggested,  for,  as  we  shall 
see,  the  readiness  with  which  they  diffuse,  for  example,  is 
of  greater  import  than  (lie  arrangemenl  of  (Ik-  atoms  which 
constitute  their  molecules. 

As  many  as  lifty  years  ago  Graham  recognized  that  dif- 
ferent chemical  substances  differ  greatly  in  the  rate  with 
which  they  diffuse  through  solvents  of  various  kinds.  Th<>se 
which  diffuse  very  slowly  are  h  r  the  most  part  amorphous, 


252  PHYSIOLOGY  OF  ALIMENTATION. 

and  since  ordinary  glue  is  an  example  of  such  he  called  the 
substances  belonging  to  this  class  colloids.  On  the  other 
hand,  those  which  diffuse  rapidly  he  called  crystalloids,  for  the 
bodies  belonging  in  this  class  are  mostly  crystalline,  as  sugar 
and  salt.  From  the  physiological  standpoint  of  absorption 
this  difference  in  the  rates  of  diffusion  still  stands  as  one  of 
the  most  important  differences  between  these  two  classes  of 
compounds,  for,  as  we  shall  see,  our  food  is  made  up  to  a 
large  extent  of  typical  representatives  of  these  classes. 

Modern  advances  in  physical  chemistry  have  given  us 
other  criteria  besides  differences  in  the  rates  of  diffusion  and 
in  their  amorphous  or  crystalline  constitution  by  which  we 
can  distinguish  between  colloids  and  crystalloids.  When 
dissolved  in  water  or  other  solvents  the  colloids  do  not  form 
true  solutions,  but  remain  suspended  in  the  liquid.  Colloidal 
solutions  are,  therefore,  heterogeneous.  More  correctly  put, 
a  colloidal  solution  represents  a  mixture  of  two  substances 
which  are  only  partially  soluble  in  each  other.  We  formerly 
looked  upon  crystalloidal  solutions  as  homogeneous.  Re- 
cent experiments  indicate,  however,  that  these  too  are  hetero- 
geneous, only  much  less  markedly  so  than  the  colloidal  solu- 
tions. 

Solutions  of  crystalloids  show  an  osmotic  pressure  which 
is  proportional  to  the  number  of  particles  of  dissolved  sub- 
stance contained  in  the  unit  volume  of  the  solvent.  As 
will  be  seen  later  it  is  upon  this  fact  as  well  as  upon  the  minute- 
ness of  the  dissolved  particles  that  the  great  diffusibility  of 
the  crystalloids  depends.  In  contrast  herewith  the  so-called 
"  typical "  colloids  show  no  osmotic  pressure  and  in  conse- 
quence do  not  diffuse  at  all.  But  only  very  few  "typical" 
colloids  exist;  the  vast  majority  show  some  osmotic  pres- 
sure and  some  diffusibility,  even  though  it  be  but 
slight. 

These  enormous  differences  in  osmotic  pressure  between 
crystalloids  and  colloids  correspond  to  similar  differences  in 
the  molecular  weight  of  the  substances  composing  the  two 


ALIMENTARY   TRACT  AS  AN  ABSORPTIVE  SYSTEM.  2.*»3 

classes.     While  the   molecular  weighl    of  mosl    crystalloids 

is  relatively  low,  that  of  the  colloids  is  very  high.  The  mo- 
lecular weight  of  glue  is,  for  example,  about  G000,  that  of 
colloidal  tungstic  acid    1700. 

The  following  (able1  shows  most  clearly  how*  a  high  molec- 
ular weight  and  osmotic  activity  are  antagonistic  values. 
The  figures  refer  to  10  percent  solutions  of  the  various  sub- 
stances. 


Substance 

Mol.  Wt. 

Osmotic  Pres- 
sure in  Atmos- 
pheres. 

Depression  of 
Freezing-point. 

Methyl  alcohol.  .         

32 

60 

ISO 

342 

2400 

13000 

70.00 

37 .  34 

12.43 

6.54 

0.93 

0.17 

5.781 

Urea     . .         

3.084 

Glucose 

1.027 

0540 

Albumose 

0.078 

Albumin 

0.015 

Crystalloids  can,  moreover,  diffuse  uninterruptedly  through 
colloidal  membranes,  such  as  animal  bladders,  intestines, 
sheets  of  agar-agar,  or  gelatine,  etc.  Colloids  are  for  the 
most  part  unable  to  do  this.  Upon  this  fact  is  based  the 
principle  of  dialysis,  in  which  crystalloids  are  separated  from 
colloids  by  placing  the  mixture  in  a  tube  of  parchment  or 
an  animal  bladder,  and  hanging  the  whole  in  water  or  some 
other  solvent.  The  crystalloids  diffuse  out,  leaving  the 
colloids  behind. 

It  must  be  pointed  out  at  once,  however,  that  no  sharp 
line  exists  between  the  colloids,  on  the  one  hand,  and  the 
crystalloids,  on  the  other.  Between  the  two  extremes  rep- 
resenting the  typical  members  of  these  groups  there  are 
found  an  infinite  number  of  substances,  which  lean  more  or 
less  strongly  toward  one  side  or  the  other.  To  illustrate 
this  fact  we  need  only  mention  thai  nol  every  crystalloid 
diffuses  through   animal   membranes,   and   not    every   colloid 


1  Hober:  Zelle  und  Gewebe.     Leipzig,  1902,  p.  19. 


+- 


254  PHYSIOLOGY  OF  ALIMENTATION. 

is  incapable  of  doing  so.  Moreover,  certain  colloids  may  be 
obtained  artificially,  not  only  in  an  amorphous  state  but 
also  in  a  most  beautifully  crystalline  form  (Hofmeister). 

So  far  as  absorption  is  concerned,  we  can  say  that  nearly 
every  food  which  enters  the  alimentary  tract  belongs  in  one 
or  the  other  of  these  two  groups,  or  does  so  after  it  is  acted 
upon  by  the  digestive  juices.  As  examples  of  the  colloids 
we  may  mention  all  the  different  albumins,  glohnlins  jaUflfc 
minakLs,  and  starch  paste:  under  the  crystalloids,  the  vari- 
ous  sugars,  salts,  acids,  and  alkalies.  We  begin  to  see  now 
the  importance  of  the  various  digestive  processes  which  go 
on  in  the  intestine.  While  it  will  be  shown  later  that  albu- 
mins, for  instance,  may  perhaps  be  absorbed  as  such,  possibly 
are  even  absorbed  in  part  in  an  unaltered  state,  it  is  self 
evident  that  as  these  colloids  become  more  like  crystalloids 
their  diffusibility,  and  in  consequence  their  absorption,  will 
be  greatly  facilitated.  In  the  process  of  digestion  this  trans- 
ference from  the  side  of  the  non-diffusible  colloids  to  that  of 
the  diffusible  crystalloids  does  in  fact  occur.  The  peptones  are 
much  less  colloidal  in  character  than  the  albumins  from  which 
*hey  come,  and  the  ultimate  products  of  digestion  formed 
under  the  influence  of  the  proteinases  or  protease  are  prac- 
tically all  typical  crystalloids.  Starch  paste  also  leaves  the 
side  of  the  colloids  when  acted  upon  by  amylase  and  as  mal- 
tose becomes  grouped  with  the  crystalloids.  The  fats  which 
as  such  are  incapable  of  diffusion  diffuse  readily  after  having 
been  acted  upon  by  lipase  and  changed  into  fatty  acid  and 
glycerine. 

3.  Membranes. — We  shall  consider  next  not  the  forces  that 
bring  about  absorption,  which  would  seem  most  logical,  but 
rather  the  obstacles  which  modify  absorption — namely,  mem- 
branes of  all  kinds.  This  will  make  what  is  to  follow  more 
intelligible. 

As  we  are  interested  in  membranes  chiefly  from  the  stand- 
point of  whether  they  allow  substances  to  diffuse  through 
them  or  not  and  to  what  extent  they  permit  this,  the  classifi- 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  255 

cation  into  s<  u/ i permeable  and  permeable  membranes  is  prob- 
ably best  suited  for  our  purposes. 

A  true  semipermeable  membrane  is  one  which  allows  only 
the  solvent  and  none  of  the  substances  dissolved  in  the  solvent 
to  pass  through.  True  semipermeable  membranes  are  really 
very  rare.  The  existence  of  such  membranes  was  discovered 
by  Traube,  but  we  are  indebted  to  Pfeffer  for  the  idea  of 
supporting  these  in  unglazed  vessels  of  earthenware,  so  that 
accurate  studies  of  them  could  be  made.  The  nature  of  true 
semipermeable  membranes  may  be  made  somewhat  clearer 
if  the  method  of  making  a  so-called  precipitation  membrane 
is  described. 

An  ordinary  Pasteur-Chamberland  filter  is  sawed  in  half 
transversely  (see  Fig.  28,  p.  263).  The  resulting  small  clay 
cylinder  after  proper  washing  is  filled  with  a  solution  of 
copper  sulphate,  and  the  whole  is  then  dipped  into  a  second 
vessel  containing  a  potassium  ferrocyanide  solution.  The  two 
solutions  penetrate  the  unglazed  clay  wall  from  opposite 
sides,  meeting  in  the  middle,  where  a  precipitate  of  copper 
ferrocyanide  is  produced. 

This  precipitate  of  copper  ferrocyanide  constitutes  a  semi- 
permeable membrane,  that  is,  one  which  is  permeable  to 
water  but  not  to  substances  dissolved  in  the  water.  We 
must  point  out  at  once,  however,  that  this  statement  is  not 
strictly  true.  It  is  true  for  the  salts  which  have  been  used  to 
produce  the  precipitation  membrane,  but  a  certain  amount 
of  nearly  all  other  sub-stances  can  pass  through  such  a  mem- 
brane. Strictly  speaking,  therefore,  even  the  semiperme- 
able membranes  are  permeable  to  some  extent,  though,  as 
we  shall  see,  not  at  all  to  the  same  degree  as  the  truly  perme- 
able membranes.  Other  precipitates  have  also  been  used  as 
semipermeable  membranes,  such  as  zinc  ferrocyanide  and 
calcium  phosphate,  but  copper  ferrocyanide  is  perhaps  the 
best. 

Almost  any  one  of  the  animal  membranes,  such  as  the 
bladder  of  various  animals,  portions  of  intestine,  or  ordinary 


256  PHYSIOLOGY  OF  ALIMENTATION. 

parchment  paper,  may  be  taken  as  a  type  of  a  permeable 
membrane.  By  this  is  meant  that  these  allow  most  crystal- 
loids which  are  held  back  by  semipermeable  membranes  to 
pass  through  them  with  ease.  But  substances  having  a  high 
molecular  weight  (as  the  various  colloids)  pass  through  these 
membranes  not  at  all  or  only  to  a  slight  extent. 

Do  true  semipermeable  membranes  exist  in  the  animal 
organism?  So  far  as  we  know  they  do  not.  Many  cells 
are  impermeable  to  a  large  number  of  substances,  but  all  are 
permeable  to  some  dissolved  substances.  The  red  blood- 
corpuscles,  for  example,  are  impermeable  to  many  different 
salts,  but  they  readily  allow  ammonium  compounds,  urea, 
etc.,  to  pass  into  them.  The  majority  of  cells  are  even  more 
permeable  than  the  red  blood-corpuscles,  and  this  even  to 
very  large  molecules.  The  fact  that  colloids  can  to  some 
extent  diffuse  into  other  colloids  already  points  in  this  direc- 
tion, and  later  we  shall  become  acquainted  with  experiments 
in  which  colloidal  sodium  silicate  was  found  to  be  absorbed 
from  the  intestinal  tract  and  excreted  in  the  urine.  The 
intestinal  epithelium  must  therefore  be  looked  upon  as  made 
up  of  cells  which  are  permeable  to  at  least  certain  very  large 
molecular  aggregates,  if  only  sufficient  time  be  allowed  for 
their  absorption.  But  the  intestinal  epithelium  is  not  equally 
permeable  to  all  substances,  even  when  they  possess  approx- 
imately the  same  molecular  weight,  and  show  in  pure  sol- 
vents approximately  the  same  rates  of  diffusion.  What  is 
true  for  the  intestinal  epithelium  holds  still  more  when  we 
deal  with  different  tissues.  Each  tissue  varies  in  the  ease 
with  which  it  will  absorb  different  chemical  compounds.  This 
selective  permeability  is  probably  more  confusing  in  endeav- 
oring to  unravel  the  problem  of  absorption  than  any  one 
other  factor,  though,  as  will  be  seen  shortly,  great  strides 
have  been  made  in  the  solution  of  this  problem  within  the 
last  decade. 

We  have  not  as  yet  said  where  these  different  membranes 
exist  in  tissues.     Every  cell  is  surrounded  by  a  membrane, 


ALIMENTARY   TRACT  AS  AN  ABSORPTIVE  SYSTEM.  257 

but  the  'physiological  membrane  with  which  we  arc  dealing 
here  need  not,  and  in  fact  usually  does  not,  coincide  with  the 
morphological  cell-wall.  This  is  shown  particularly  well  in 
vegetable  cells  in  which  the  physiological  membrane  lies 
entirely  within  the  morphological  membrane.  Certain  cells 
do  not  have  any  morphological  membrane  at  all,  yet  a  physio- 
logical membrane  permeable  to  certain  substances  and  im- 
permeable to  others  no  doubt  exists  in  these  cases.  This  is 
so,  for  example,  in  the  red  blood-corpuscles,  in  amoebae,  and 
in  the  intestinal  epithelium.  Finally,  when  we  deal  with 
tissues,  whole  cells  arranged  in  layers  may  constitute  a  mem- 
brane through  which  diffusion  occurs  from  one  medium  into 
another.  Under  these  circumstances  the  protoplasm  of  the 
cell,  as  a  whole,  constitutes  the  membrane. 

What  has  been  said  of  the  cells  themselves  holds  true  also 
for  groupings  of  these  cells  as  they  exist  in  the  various  mem- 
branes of  the  body — such  as  the  absorptive  mucous  mem- 
branes of  the  alimentary  and  urinary  tracts,  the  synovial 
membranes,  etc.  As  the  individual  cells  differ  from  each 
other  in  permeability,  so  do  also  the  various  tissues  built  up 
of  these  cells.  In  dealing  with  tissues  we  have  yet  to  take 
into  consideration  the  permeability  of  the  intercellular  sub- 
stance. This  may  be  entirely  different  from  the  permeability 
of  the  cells  themselves. 

4.  The  Forces  Active  in  Absorption. — If  an  odorous  gas 
is  liberated  in  one  corner  of  a  room,  it  soon  spreads  through- 
out the  whole  room,  so  that  it  may  be  detected  anywhere  in 
it.  We  say  that  the  gas  diffuses  through  the  room,  and, 
according  to  the  kinetic  theory,  this  diffusion  takes  place 
because  the  molecules  <^  the  gas  are  in  constant  motion  and 
move  in  all  directions.  The  odorous  gas  continues  to  diffuse, 
if  nothing  prevents  it .  until  the  concent  rat  ion  of  this  substance 
IS  the  same  in  all  portions  of  the  room. 

If  a  substance    (such  a  copper    sulphate)   is    put   into  a 

vessel  and  a  solvent  (such  as  distilled  water)  is  carefully 
poured  upon  it,  we  find  thai   after  a  while  the  soluble  sub- 


258  PHYSIOLOGY  OF  ALIMENTATION. 

stance  has  distributed  itself  uniformly  throughout  the  solu- 
tion. We  say  that  the  soluble  substance  has  diffused  through 
the  solvent.  This  process  of  diffusion  is  analogous  to  the 
diffusion  of  gases  described  in  the  preceding  paragraph. 
When  a  crystal  of  copper  sulphate  is  covered  with  pure  water, 
the  diffusion  of  the  copper  salt  shows  itself  as  a  blue  zone 
about  the  crystal,  which  gradually  spreads  until  all  the  water 
is  tinged  uniformly  blue  and  the  crystal  (provided  it  has  not 
been  too  large)  has  entirely  disappeared.  It  is  not  necessary 
to  start  with  a  crystal  of  the  copper  sulphate, — a  solution  of 
this  salt  may  be  used  instead  and  it  be  carefully  covered 
with  distilled  water.  Diffusion  occurs  in  the  same  way  and 
continues  until  the  entire  volume  of  water  is  tinged  uni- 
formly blue.  What  has  been  said  holds  for  any  solvent  and 
any  soluble  substance,  be  the  latter  a  solid,  a  liquid,  or  a  gas. 

What  is  the  cause  of  this  movement  of  particles  of  dis- 
solved substance  from  places  of  higher  concentration  to  places 
of  lower  concentration,  in  other  words,  this  diffusion? 

In  the  case  of  the  odorous  gas  liberated  in  a  room,  we 
attribute  the  spread  of  the  odorous  substance  throughout  the 
room  to  the  fact  that  its  partial  pressure  is  greater  at  the 
point  of  liberation  than  anywhere  else  in  the  room.  In  other 
words,  the  gas  pressure  is  highest  where  the  odorous  sub- 
stance is  liberated,  and  in  consequence  the  odorous  particles 
of  gas  are  driven  through  the  room  until  the  pressure  is  every- 
where the  same.  Entirely  analogous  to  the  movement  of 
the  particles  of  a  gas  through  a  vacuum  or  another  gas  is  the 
movement  of  the  particles  of  a  dissolved  substance  through 
a  solvent,  only,  while  we  call  the  force  which  causes  the  move- 
ments of  a  gas,  gas  pressure,  we  call  the  force  which  causes 
the  movement  of  a  dissolved  substance  osmotic  pressure. 
Just  as  a  gas  exerts  a  certain  (gas)  pressure  upon  the  walls 
of  its  container,  so  a  dissolved  substance  exerts  a  certain 
(osmotic)  pressure  upon  the  walls  of  its  container.  This 
pressure,  indicative  of  the  movement  of  the  dissolved  sub- 
stance, we  can  render  apparent  by  separating  the  region  of 


ALIMENTARY   TRACT  AS  AX  ABSORPTIVE  SYSTEM.  259 

higher  concentration  from  that  of  lower  concentration  by  a 

semipermeable  membrane.  As  was  pointed  OUl  before,  this 
means  a  membrane  which  will  not  give  passage  to  a  dis- 
solved substance  but  only  to  its  solvent.  The  dissolved 
substance  in  its  movement  through  (he  solvent  is  I  hen  slopped 
by  this  wall,  in  consequence  of  which  it  exerts  a  pressure 
(osmotic  pressure)  upon  it  which  evidences  itself,  if  the 
membrane  is  not  so  supported  as  to  prevent  it,  by  a  bulging 
of  the  membrane  toward  the  region  of  lower  osmotic  pres- 
sure. 

Just  as  gas  pressure  varies  with  different  external  con- 
ditions, so  does  osmotic  pressure  (van't  Hoff).  Of  great 
physiological  importance  is  the  fact  that  at  constant  tem- 
perature the  osmotic  pressure  of  dilute  solutions  is  proportional 
to  the  concentration  of  the  dissolved  substance.  By  the  con- 
centration of  the  dissolved  substance  is  meant  the  number 
of  particles  of  this  substance  contained  in  the  unit  volume. 
This,  the  first  law  of  van't  Hoff,  means  that  if  a  solution  of 
a  certain  concentration  has  a  certain  osmotic  pressure,  the 
osmotic  pressure  will  be  doubled  if  in  the  same  volume  of 
solvent  twice  the  amount  of  soluble  substance  be  dissolved, 
or  trebled  if  three  times  the  original  amount  goes  into  solu- 
tion in  it  (see  below), 

Van't  Hoff  's  second  law  is  also  of  physiological  importance. 
The  osmotic  pressure  of  a  dilute  solution  is  proportional  to  the 
absolute  temperature,  in  other  words,  increases  as  the  tem- 
pera! ure  is  increased,  even  when  all  other  external  conditions, 
are  left  unchanged.  The  third  law  of  van't  Hoff,  (hat  at 
the  same  temperature  eejnol  ml  nines  of  all  dilute  solutions  which 
have  the  same  osmotic  pressure  contain  the  same  number  of 
molecules  does  not  interest  us  in  a  discussion  of  the  immediate 
problem. 

We  have  purposely  spoken  above  of  the  osmotic  pressure 
of  dissolved  particles.  We  can  say  now  thai  wherever  this 
term  has  been  used  above  we  may  substitute  the  word 
molecules,    but    this   only   when    the   substance    under   con- 


260  PHYSIOLOGY  OF   ALIMENTATION. 

sideration  is  a  so-called  non-electrolyte,  that  is,  a  substance 
which  in  solution  in  water  does  not  conduct  the  electric  cur- 
rent. Into  this  group  cf  non-electrolytes  belong,  for  ex- 
ample, the  various  sugars,  glycerine,  and  urea.  Under  the 
electrolytes  are  classed  all  those  substances  which  when  dis- 
solved in  water  conduct  the  electric  current.  This  group  is 
composed  of  the  acids,  bases,  and  salts,  the  more  typical 
examples  being  the  strong  acids,  bases,  and  salts,  such  as  the 
mineral  acids,  the  caustic  alkalies,  and  the  salts  formed  by 
the  chemical  union  of  these  two. 

Van't  Hoff's  laws  do  not  hold  in  this  unmodified  way  for 
the  electrolytes.  Solutions  of  electrolytes  all  behave  as 
though  they  contained  a  larger  number  of  molecules  than  is 
indicated  by  the  weight  of  the  substance  dissolved  in  the 
water.  This  apparent  exception  to  the  laws  of  van't  Hoff 
has  been  explained  by  Arrhenius,  who  has  shown  that  when 
electrolytes  are  dissolved  in  water  the  molecules  break  up 
into  smaller  electrically  charged  atoms  or  groups  of  atoms 
called  ions.  This  theory  of  ions  is  also  known  as  the  theory 
of  electrolytic  dissociation.  The  degree  of  dissociation  or 
ionization  which  the  molecules  of  an  electrolyte  undergo 
varies  not  only  with  the  nature  of  the  electrolyte  itself,  but 
also  with  a  number  of  external  conditions  such  as  tempera- 
ture, concentration,  etc.  But  the  amount  of  this  dissocia- 
tion can  be  determined  experimentally,  and  when  it  is  taken 
into  consideration  the  laws  of  van't  Hoff  are  valid  for  solu- 
tions of  electrolytes  also.  Modified  in  this  way  the  first  law  of 
van't  Hoff  reads:  The  osmotic  pressure  of  a  solution  is  pro- 
portional to  the  number  of  molecules  plus  ions  present  in  the 
unit  volume  of  solvent.  The  word  particles  was  used  above 
to  cover  this  conception  of  molecules  plus  ions. 

What  has  been  said  will  serve  to  indicate  the  important 
role  which  diffusion  must  play  in  determining  the  migration 
of  dissolved  substances  from  regions  of  higher  concentration 
to  those  of  lower.  Because  of  diffusion  the  sugars,  the  salts, 
and  the  digestion  products  of  the  proteins  and  fats  enter  the 


ALIMENTARY    Tit  ACT  As   AN  ABSORPTIVE  SYSTEM.  261 

intestinal  mucosa  and  pass  into  the  blood  and  lymph  Streams. 
The  process  of  diffusion  within  the  animal  organism  does  not 
go  on  as  simply  and  as  uninterruptedly,  however,  as  in  a 
vessel  containing  a  solvent  and  a  soluble  substance.  The 
rate  of  entrance  of  even  the  simplest  chemical  substances 
into  the  epithelial  cells  of  the  intestinal  mucosa  is  far  dif- 
ferent from  the  rates  of  diffusion  of  these  same  substances 
outside  of  the  body.  As  will  become  apparent  later  an 
important  reason  for  this  is  to  be  found  in  the  constitution  of 
protoplasm  itself,  and  of  the  membranes  surrounding  this 
protoplasm. 


CHAPTER  XV. 

THE   ALIMENTARY    TRACT   AS   AN    ABSORPTIVE    SYSTEM 

(Continued). 

5.  The  Absorption  of  Water. — What  has  gone  before  in- 
dicates how  osmotic  pressure  is  one  of  the  forces  which  deter- 
mines the  movement  of  dissolved  substances.  It  will  be 
shown  now  that  under  proper  conditions  it  becomes  a  force 
which  determines  the  movement  of  water,  and  that  it  is  in 
part  responsible  for  the  absorption  of  this  substance  in  the 
living  organism.  The  amount  of  water  that  can  be  absorbed 
from  the  alimentary  tract  is  enormous.  It  is  ordinarily- 
stated  that  4  or  5  liters  of  pure  water  may  be  absorbed  in  the 
course  of  a  day.  This  does  not,  however,  indicate  all  that 
can  be  absorbed.  Friedrich  Muller  once  showed  in  his  clinic 
in  Munich  a  man  who  not  infrequently  consumed  between  20 
and  30  liters  of  beer  in  twenty-four  hours  without  having  a 
diarrhcea.  Beer  does  not,  of  course,  represent  pure  water, 
and  the  limits  for  this  substance  may  be  lower. 

Osmotic  pressure  becomes  effective  in  determining  the 
absorption  of  water  when  the  diffusion  of  the  dissolved  parti- 
cles to  regions  of  a  lower  concentration  is  prevented  by  a 
semi-permeable  membrane.  This  may  be  illustrated  by  the 
accompanying  diagram  (Fig.  28).  A  represents  in  cross- 
section  a  Pasteur-Chamberland  filter,  in  the  wall  of  which 
is  deposited  a  semipermeable  precipitation  membrane  M ,  such 
as  copper  ferrocyanide,  made  as  described  above  (page  255). 
The  osmotic  cell,  as  such  an  apparatus  is  called,  is  closed  with  a 
rubber  stopper,  C,  through  which  passes  the  glass  manometer 

262 


ALIMENTARY   TRACT  AS  AN  ABSORPTIVE  SYSTEM    263 

tube  T.  If  this  cell  is  filled  with  a  sugar  solution,  and  the 
whole  is  dipped  into  a  second  vessel,  H,  filled  with  water,  the 
sugar  endeavors  to  pass  out  into  the  wider  (diffusion).  This 
movement   is   prevented,    however,    by   the   semipermeable 


...  ,  ., 


Sugar 
Solution 


Water 


Fig.  28. 


membrane  and  water  is  in  consequence  drawn  into  the 
osmotic  cell,  which  evidences  itself  by  a  rise  of  the  meniscus 
in  the  tube  T.  The  water  continues  to  enter  the  cell  until 
the  hydrostatic  pressure  in  the  lube  is  equal  to  the  osmotic 
pressure  in  the  cell. 

The  reason  why  the  water  enters  the  cell,  or,  in  general, 


264 


PHYSIOLOGY  OF  ALIMENTATION. 


why  water  moves  from  a  region  of  lower  concentration  to 
one  of  higher,  is  not  yet  entirely  understood.  The  old  idea 
was  that  the  dissolved  particles  "attracted"  the  water.  A 
more  correct  explanation  of  the  phenomenon  based  upon 
differences  in  surface  tension  seems  to  be  the  following. 
Liquids  (water  in  this  case)  are  surrounded  by  a  contractile 
surface  film,  in  consequence  of  which  they  always  tend  to 
occupy  as  small  a  space  as  possible  (that  is,  tend  to  become 
spherical).  These  surface  films,  therefore,  exert  a  pressure 
in  a  direction  toward  the  centre  of  the  liquid,  as  shown  in 
Fig.  29,  a.  The  pressure  exerted  by  the  diffusion  of  dissolved 
particles  is  evidently  opposite  in  nature  to  that  exerted  by 


Fig.  29. 

such  surface  films,  for  the  particles  of  a  dissolved  substance 
move  from  the  centre  toward  the  surface  of  a  liquid  and 
press  upon  it.  This  is  indicated  in  Fig.  29,  b.  In  the  vessel 
B  in  Fig.  28,  which  contains  only  pure  water,  we  are  dealing 
with  surface  tension  only,  which  we  will  represent  by  P. 
In  the  osmotic  cell  we  have  this  same  surface  tension,  but  it 
is  counteracted  by  the  osmotic  pressure  p.  Evidently,  there- 
fore, PyP—f.  Or,  to  put  the  same  in  words,  the  surface 
tension  of  the  water  outside  of  the  cell  is  greater  than  the 
surface  tension  inside  of  the  cell  minus  the  osmotic  pressure. 
Water  passes  from  the  outer  vessel  into  the  cell,  therefore, 
because  it  is  squeezed  in  and  not  because  it  is  pulled  in. 

It  is  clear  that  what  has  been  said  regarding  pure  water 


ALIMENTARY   TRACT  AS  AN  ABSORPTIVE  SYSTEM.  265 

and  a  sugar  solution  holds  for  any  pure  solvent  and  any  solu- 
tion. Furthermore,  it  holds  for  any  two  solutions  which 
have  not  the  same  osmotic  pressure  (that  is  to  say,  have  no! 
the  same  number  of  particles  dissolved  in  the  unit  volume 
of  solvent).  The  solvent  moves  always  from  the  region  of 
lower  concentration  to  that  of  higher  concentration  (thai  is, 
from  the  region  of  lower  osmotic  pressure  to  the  region  of 
higher)  when  the  two  are  separated  by  a  semipermeable 
membrane,  and  this  movement  continues  until  the  osmotic 
pressure  on  both  sides  is  the  same.  It  is  clear,  therefore, 
that  if  the  osmotic  cell  is  filled  with  water  instead  of  with  a 
sugar  solution  and  the  surrounding  vessel  contains  a  sugar 
solution,  or,  to  put  it  more  generally,  if  the  osmotic  cell  con- 
tains a  solution  of  a  lower  concentration  than  the  surrounding 
vessel,  the  water  will  move  out  of  the  cell  into  the  solution  in 
the  outer  vessel  until  the  osmotic  pressure  on  both  sides  of 
the  membrane  is  again  the  same. 

Do  similar  conditions  exist  in  the  case  of  the  body  cells? 
To  a  certain  extent  they  do.  It  was  pointed  out  above  that 
many  cells  which  have  been  studied  seem  to  be  surrounded 
by  membranes  which  have  to   be  considered    as    approxi- 


mating true  semipermeable  ones  more  or  less  perfectly. 
Certain  cells  even  seem  to  possess  membranes  which  arc  truly 
semipermeable  for  a  large  Dumber  of  substances.  Fig.  30 
illustrates  the  behavior  of  any  cell  possessing  a  truly  semi- 
permeable membrane  towards  solutions  *>(  various  kinds. 
If  we  consider  b  the  cell  under  normal  physiological  con- 


266  PHYSIOLOGY  OF  ALIMENTATION. 

ditions,  that  is,  as  in  osmotic  equilibrium  with  the  liquids 
with  which  it  is  bathed,  then  a  and  c  represent  respectively 
the  effect  upon  this  cell  of  immersion  in  a  solution  more 
dilute  or  more  concentrated  than  that  in  which  it  is  immersed 
normally.  If  the  cell  is  placed  in  a  solution  which  has  a 
lower  osmotic  pressure  than  the  cell  contents,  then  water 
will  pass  into  the  cell  until  the  osmotic  pressure  on  both  sides 
of  the  (physiologically)  semipermeable  membrane  is  the  same. 
The  cell  will  in  consequence  increase  in  size  (if  some  external 
obstacle  does  not  prevent  it)  and  may  swell  so  much  that 
the  cell-wall  is  ruptured  and  the  cell  contents  are  allowed 
to  escape.  The  reverse  must  occur  when  the  cell  is  immersed 
in  a  fluid  having  a  higher  osmotic  pressure  than  the  cell 
contents.  Under  these  circumstances  water  passes  through 
the  semipermeable  membrane  surrounding  the  cell  in  the 
direction  from  within  outwards  until  osmotic  equilibrium 
is  once  more  restored.  As  the  water  passes  out  of  the  cell, 
this  shrinks,  and  the  amount  of  the  shrinkage  is  determined 
by  the  amount  of  water  given  off  by  the  cell.  This  in  turn 
is  determined  by  the  amount  of  the  difference  between  the 
osmotic  pressure  of  the  cell  contents  and  that  of  the  sur- 
rounding liquid. 

True  semipermeable  membranes  are  rarely  found  sur- 
rounding any  cells  that  have  been  accurately  studied,  and 
so  it  will  not  seem  strange  that  physiological  experiment 
has  shown  that  the  epithelial  cells  of  the  alimentary  tract 
obey  the  ordinary  laws  governing  the  osmotic  absorption 
of  water  only  when  exposed  to  great  and  sudden  changes 
by  being  flooded  with  solutions  of  very  high  or  very  low 
osmotic  pressures.  The  reason  for  this  is  readily  intelligible 
when  it  is  remembered  how  very  permeable  the  alimentary 
mucosa  must  be  to  allow  the  passage  of  the  host  of  soluble 
substances  which  daily  pass  through  it  into  the  blood  or 
lymph  or  from  these  circulating  fluids  out  into  the  lumen 
of  the  digestive  tube.  Whenever  a  membrane  allows  the 
passage  of  a  substance  dissolved  in  a  liquid  found  on  either 


ALIMENTARY  TRACT   AS     I.V  ABSORPTIVE  SYSTEM.   2G7 

side  of  it,  Him  differences  in  osmotic  pressure  are  quickly 
equalized  through  diffusion  of  the  dissolved  particles,  and  a 
movement  of  water  can  in  consequence  show  itself  only 
imperfectly. 

But  the  cells  of  the  alimentary  mucosa  are  by  no  means 
equally  permeable  to  nil  dissolved  substances.  For  this  rea- 
son the  cells  of  the  alimentary  tract  (as  well  as  other  body 
cells)  obey  the  laws  of  osmotic  pressure  more  perfectly  when 
certain  substances  are  dissolved  in  the  fluids  present  in  the 
alimentary  tract  than  when  others  are  concerned.  A  partial 
explanation  at  least  of  this  selective  permeability  of  cells  will 
be  given  when  we  discuss  Overton  and  Meyer's  work  on  the 
lipoids. 

We  have  yet  another  way  of  influencing  the  absorption  of 
wrater  besides  through  differences  in  osmotic  pressures,  and 
that  is  by  changes  in  the  affinity  of  the  colloids  for  water.  As 
is  well  known  protoplasm  is  composed  of  a  mixture  of  col- 
loids^ and  experiment  has  shown  that  the  amount  of  water 
absorbed  by  colloids  can  be  enormously  influenced  by  a  num- 
ber of  external  conditions.  As  shown  by  such  experiments 
as  those  of  Hofmeister,1  gelatine  plates  absorb  water  from 
the  chlorides  of  the  alkali  metals.  They  absorb  much  more 
from  isotonic  solutions  of  the  bromides  and  nitrates  of  these 
same  metals.  The  citrates,  sulphates,  and  tartrates  of  these 
metals,  on  the  other  hand,  cause  such  swollen  plates  to  give  up 
their  water.2  It  almost  seems  as  though  in  an  understanding 
of  the  laws  governing  the  absorption  of  liquids  by  colloids,  and 
of  the  secretion  of  these  same  liquids  when  external  con- 
ditions are  slightly  altered,  lies  the  explanation  of  much  that 
is  obscure  in  the  phenomena  of  absorption  and  secretion  as 
they  are  found  in  the  animal  and  vegetable  organism. 
Chanu'es  in  osmotic  pressure  are  certainly  by  themselves  in- 


1  Hofmeistkr:   Aicliiv  f.  oxp.  Patli,  XXVIII,  p.  210. 
'This  almost   seems  analogous  t<>  1 1 1<>  secretion  <>i  water  into  the 
alimentary  tract  under  the  influence  of  cathartic  salts. 


268  PHYSIOLOGY  OF  ALIMENTATION. 

adequate  to  explain  more  than  a  few  of  the  facts  observed 
experimentally  in  these  fields.  Perhaps  pathology  may  also 
find  help  here.1 

6.  Lipoidal  Absorption. — If  a  cell  (such  as  a  red  blood- 
corpuscle)  possessing  a  semipermeable  membrane  is  put  into 
a  series  of  differently  concentrated  solutions  of  a  certain 
substance  it  will  show  no  change  in  volume  (will  not  shrink 
or  swell)  in  that  solution  which  has  the  same  osmotic 
pressure  as  the  cell  contents.  Such  a  solution  is  said  to  be 
isosmotic  or  isotonic  with  the  cell  contents.  If,  now,  solutions 
of  different  substances  are  prepared  a  certain  concentration 
can  be  found  for  each  of  these  in  which  the  cell  used  for  study 


1  On  the  hypothesis  that  cedema  represents  an  increased  affinity  of 
the  colloids  of  the  tissues  for  water  brought  about  through  the  presence 
in  them  of  abnormal  substances  capable  of  increasing  this  affinity  I 
have  made  a  series  of  experiments  which  seem  to  support  this  idea. 
Not  only  does  calculation  show  that  the  maximum  amount  of  water 
ever  held  by  a  tissue  in  cedema  at  no  time  exceeds  the  amount  easily 
absorbed  by  a  gelatine  plate,  but  acids  and  certain  salts  which  increase 
the  affinity  of  gelatine  plates  for  water  increase  in  a  similar  way  the 
affinity  of  frog's  muscles,  connective  tissue,  etc.,  for  water.  In  cedema- 
tous  tissues  we  have  not  only  the  presence  of  an  increased  amount  of 
C02,  but  also  organic  acids  of  various  kinds,  and  these  present  in  con- 
centrations which  readily  increase  the  affinity  of  ordinary  gelatine  plates 
for  water  some  30  or  40  percent.  Many  poisonous  substances — such 
as  the  irritant  oils — which  by  themselves  do  not  increase  the  affinity 
of  a  gelatine  plate  for  water,  nevertheless  bring  about  an  cedematous 
swelling  when  applied  to  living  tissues,  apparently  because  they  lead 
to  an  altered  metabolism  of  the  cells  concerned  which  brings  with  it 
the  production  of  substances  which  do  increase  the  affinity  of  colloids 
for  water.  An  attempt  to  show  that  such  substances  are  present  in 
cedematous  tissues  lead  to  the  experiment  of  introducing  frog's  gas- 
trocnemii  into  the  peritoneal  cavities  of  normal  rabbits  and  rabbits  with 
an  ascites  due  to  the  injection  of  uranium  salts.  In  spite  of  the  isoton- 
icity  of  the  normal  and  abnormal  peritoneal  fluids  the  frog's  muscles 
contained  in  the  ascitic  rabbits  weighed  20  to  30  percent  more  at  the 
end  of  several  days  than  those  in  the  healthy  rabbits.  The  blood-serum 
of  an  ascitic  rabbit  will,  moreover,  upon  injection,  bring  about  an 
cedema  in  a  healthy  one. 


ALIMENTARY   TRACT  AS  AN  ABSORPTIVE  SYSTEM.  209 

shows  no  change  in  volume.  Since  ;ill  of  these  solutions 
must  then  be  isosmotic  with  the  cell  contents  they  must  also 
be  isosmotic  with  each  other.  The  red  blood-corpuscles  (and 
other  cells)  have  been  employed  in  this  way  for  the  determi- 
nation  of  osmotic  pressure.  But  this  is  true  only  when 
the  cell  has  a  true  semipermeable  membrane,  and  such 
exist  practically  nowhere  in  living  organisms.  As  the  num- 
ber of  substances  studied  with  reference  to  their  power  of 
changing  the  volume  of  red  blood-corpuscles  (or  causing  them 
to  give  up  their  red  coloring-matter  or  "plasmolyzing" 
various  plant-cells,  etc.)  increased  it  was  soon  found  that 
there  exist  a  large  number  of  substances  which  affect 
the  cells  either  at  no  concentration  at  all  or  only  when 
present  in  amounts  greatly  exceeding  the  ordinary  limits 
at  which  a  change  in  volume  might  be  expected.  Atten- 
tion was  called  to  this  fact  when  it  was  pointed  out  that  the 
cells  of  the  alimentary  mucosa  swell  or  shrink  only  when 
exposed  to  great  and  sudden  changes  in  osmotic  pressure 
through  the  fluids  surrounding  them.  These  substances 
which  in  solution  failed  to  bring  about  changes  in  the  volumes 
of  cells  in  proportion  to  their  osmotic  pressure  existed  for  a 
long  time  as  unexplained  exceptions  until  Overton  and 
Meyer  made  a  systematic  study  of  them  and  so  advanced 
most  markedly  our  knowledge  of  the  fundamental  character 
of  absorption  and  secretion.1 

The  power  of  a  solution  to  abstract  water  from  a  cell  (that 
is,  to  shrink  or  "plasmolyze"  it)  is  dependent  upon  the  semi- 
permeability  of  the  membrane  surrounding  the  cell  to  the 
substance   dissolved   in   the   solution.     If  the   substance   is 


1  Overton:  Vierteljahresschrift  d.  naturforsch.  Gesellsch.  in  Zurich, 
1895,  XL,  p.  1,  and  1S99,  XLIV,  p.  SS;  Zeits.hr.  l".  physik.  Chemie, 
1S97,  XXII,  p.  1S9.  Meyer:  Arch,  t  exp.  Path.  u.  Phann.,  l.v.t't. 
XIII,  p.  109,  and  1901,  XLVI,  p.  338.  This  accounl  is  largely  taken 
from  Hober's  excellent  Physikalische  I  Ihemie  der  Zelle  und  An-  Gewebe, 
Leipzig,  1902,  p.  101.    See  also  Spiro:    Physikalische  und  physiolo- 

gische  Selection.  St r:i>sl>urg,  IS'.iT. 


270  PHYSIOLOGY  OF  ALIMENTATION.  < 

able  to  pass  through  the  cell  membrane  plasmolysis  must 
in  consequence  be  impossible,  for  under  these  circumstances 
the  diffusion  of  the  dissolved  substance  into  the  cell  equalizes 
the  pressure  on  both  sides  of  the  membrane,  and  the  difference 
between  the  osmotic  pressure  inside  and  outside  of  the  cell 
which  is  essential  for  plasmolysis  does  not  come  to  pass.  A 
movement  of  water  does  not  occur  in  the  direction  toward 
the  region  of  higher  osmotic  pressure  as  when  a  semipermeable 
membrane  is  present,  but  a  movement  of  dissolved  particles 
takes  place  from  the  region  of  higher  osmotic  pressure  to  that 
of  lower  osmotic  pressure.  Only  in  case  the  cell  membrane 
possesses  but  a  limited  permeability  do  both  water  and  dis- 
solved substance  move,  for  in  this  case  a  cell  will  give  up 
some  of  its  water  to  the  more  concentrated  solution  surround- 
ing it  before  the  substance  dissolved  in  this  solution  has  had 
time  to  diffuse  into  the  cell.  Under  such  circumstances  a 
temporary  change  in  the  volume  of  the  cell  concerned  is  pos- 
sible. Herein  lies  the  explanation  of  the  behavior  of  the 
cells  of  the  alimentary  mucosa  in  responding  only  temporarily 
to  great  and  sudden  changes  in  the  osmotic  pressure  of  liquids 
surrounding  them. 

But  the  intensity  with  which  a  solution  can  bring  about 
the  plasmolysis  of  a  cell  is  a  function  not  only  of  the  degree 
of  difference  between  the  osmotic  pressure  without  and 
within  the  cell,  but  also  of  the  velocity  with  which  the  sub- 
stance can  penetrate  the  cell  membrane.  It  is  evident  that 
with  the  same  degree  of  osmotic  difference  a  substance  capa- 
ble of  diffusing  rapidly  into  a  cell  will  be  less  likely  to  plas- 
molyze  the  cell  than  one  which  diffuses  in  more  slowly,  for 
under  the  latter  circumstances  a  movement  of  water  is  more 
likely  to  occur  than  under  the  former. 

It  becomes  possible  to  differentiate  in  consequence  be- 
tween substances  which  enter  cells  slowly  and  those  which 
enter  rapidly.  Glycerine  belongs  to  the  class  of  substances 
which  diffuse  slowly  into  a  cell  and  as  slowly  leave  it.  If 
algse  are  in  consequence  placed  in  a  dilute  glycerine  solution 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  271 

and  the  concentration  of  this  is  allowed  to  increase  slowly 
through  evaporation  the  algse  suffer  no  change,  for  each  in- 
crease in  the  concentration  of  the  glycerine  solution  has  time 
to  be  equalized  by  an  increase  in  the  concentration  of  the 
glycerine  within  the  cell.  But  if  the  algse  be  removed  from 
the  now  concentrated  solution  of  glycerine  and  dropped  into 
clear  water  they  burst  at  once,  for  in  so  short  a  time  the 
glycerine  has  not  had  time  to  diffuse  out  of  the  cells. 

Methyl  alcohol  belongs,  on  the  other  hand,  to  the  sub- 
stances which  can  rapidly  pass  through  cell  membranes. 
The  root  hairs  of  Ht/jrocharis  plasmolyze  in  a  cane-sugar 
solution  having  a  concentration  between  7  and  1\  percent. 
Plasmolysis  occurs  in  the  1\  percent  solution  in  10  seconds. 
If  3  percent  of  methyl  alcohol  are  added  to  the  7  percent 
cane-sugar  solution  its  osmotic  pressure  is  made  to  equal  a 
35  percent  cane-sugar  solution.  Yet  in  this  mixture  of 
sugar  and  methyl  alcohol  no  plasmolysis  occurs,  for  the 
methyl  alcohol  diffuses  almost  instantaneously  through  these 
cells  so  that  the  great  difference  between  the  osmotic  pres- 
sure within  and  without  the  cells  cannot  become  effective. 
(Overton.)  1 

To  the  compounds  which  diffuse  rapidly  into  protoplasm 
belong  the  monatomic  alcohols,  aldehydes,  and  ketones,  the 
hydrocarbons  with  one,  two,  and  three  chlorine  atoms,  the 
nitroalkyls,  the  alkylcyanides,  the  neutral  esters  of  inorganic 
and  many  organic  acids,  anilin,  etc.  The  diatomic  alcohols 
and  the  amides  of  monatomic  acids  pass  into  cells  more 
slowly,  and  still  more  slowly  glycerine,  urea,  and  erythrite. 
The  hexatomic  alcohols,  the  sugars  with  six  carbon  atoms 
(hcxoses),  the  amino-acids,  and  the  neutral  salts  of  the  organic 
acids  diffuse  into  cells  only  very  slowly.  The  entrance  of 
these  various  substances  into  the  cells  is  rendered  apparent 
by  yet  other  signs  than  a  failure  of  plasmolysis,  such  as  evi- 
dence of  narcosis  or  other  intoxication,  the  formation  of  pre- 

1  Cited  from  Bober:  1.  c,  p.  105. 


272  PHYSIOLOGY  OF  ALIMENTATION. 

cipitates,  etc.,  but  the  details  of  these  experimental  findings 
must  be  sought  in  the  original  publications. 

A  simple  glance  at  the  table  given  in  the  last  paragraph 
shows  that  we  have  to  deal  with  all  manner  of  chemical  sub- 
stances, from  those  relatively  simple  in  composition  to  those 
very  complex,  some  of  physiological  importance  and  found 
as  normal  constituents  of  the  living  cell,  others  entirely 
foreign  to  the  living  organism.  What  physico-chemical 
character  have  all  these  substances  in  common  which 
allows  them  to  penetrate  living  cells  more  or  less  readily 
and  so  modify  the  otherwise  simple  osmotic  behavior  of 
cells  in  general? 

An  explanation  frequently  given  and  long  believed  to  be 
the  correct  one  is  that  the  size  of  the  molecules  is  the  con- 
dition which  determines  the  entrance  of  the  dissolved  particles. 
According  to  this  conception  the  cell  membranes  may  be 
regarded  as  sieves  which  allow  all  molecules  that  do  not 
exceed  a  certain  size  to  pass  into  the  cell,  while  those  larger 
than  this  are  held  back.  The  deficiencies  of  such  an  explana- 
tion are  at  once  apparent  when  it  is  remembered  that  mem- 
branes which  readily  give  passage  to  such  large  atomic  aggre- 
gates as  the  alkaloids  or  sodium  salicylate  hold  back  the 
much  simpler  amino  acids  and  potassium  sulphate. 

According  to  Overton  all  the  substances  enumerated  above 
enter  cells  because  the  membranes  surrounding  them  behave 
like  films  composed  of  a  substance  which  in  its  properties  as  a 
solvent  is  not  unlike  ether  or  the  fatty  oils.  For  this  reason  all 
those  substances  which  are  more  soluble  in  such  ethereal  or 
oil-like  substances  than  in  water  enter  the  cell  and  this  the 
more  rapidly  the  greater  the  solubility  of  the  substance  in 
the  ethereal  or  oil-like  substances  as  compared  with  water; 
in  other  words,  the  greater  the  distribution  coefficient  between 
the  film  surrounding  the  cell  and  water.  This  distribution 
coefficient  is,  at  the  same  temperature,  independent  of  the 
concentration  of  the  substance.  This  means  that  if  a  sub- 
stance soluble  in  any  two  solvents  is  offered  these  simulta- 


ALIMENTARY  TRACT  AS   AN   ABSORPTIVE  SYSTEM.   273 

oeously  (for  example,  .succinic  acid  to  a  mixture  of  equal  parts 
of  water  ami  ether)  the  proportion  of  this  substance  found 
in  solul  ion  in  each  of  the  solvents  will  always  be  the  same  no 
mat  ler  how  much  of  the  substance  is  offered  the  two  solvents. 
This  means  that  if  of  six  grams  of  succinic  acid  offered  a 
certain  volume  of  ether  and  water,  five  grams  are  found  to 
1  issolve  in  the  ether  and  one  in  the  water,  then  if  twelve  grams 
I)  -  offered  the  two  solvents,  ten  will  dissolve  in  the  ether  and 
t  wo  in  the  water.  The  proportion  of  5  :  1  is  therefore  main- 
tained.1 

With  these  ideas  in  mind  it  is  only  necessary  to  reexamine 
the  list  of  substances  which  experiment  has  shown  enter 
cells  more  or  less  rapidly  and  see  if  they  are  not  all  of 
a  character  which  are  more  soluble  in  ethereal  or  oily  sub- 
stances than  in  water,  and  that  those  which  stand  first  in  the 
list  and  consequently  enter  cells  most  rapidly  are  not  such 
as  have  the  highest  distribution  coefficients.  An  illustration 
may  make  this  clearer.  The  repeated  substitution  of  an 
at  "in  or  a  group  of  atoms  for  some  other  atom  or  group  of 
at "ms  in  a  chemical  compound  is  often  accompanied  by 
marked  changes  in  the  solubility  of  this  compound  and  its 
derivatives.  Glycerine  enters  a  cell  only  very  slowly.  When 
an  atom  of  chlorine  is  introduced  into  this  compound  it 
enters  protoplasm  more  rapidly,  and  when  two  are  introduced 
still  more  rapidly,  for  these  derivatives  are  more  readily 
soluble  in  fats  than  the  original  glycerine.  The  same  holds 
true  of  urea  and  its  methylated  derivatives.  While  urea 
diffuses  but  slowly  into  cells,  the  introduction  of  one,  two, 
or  three  methyl  radicles  into  this  compound  increases  pro- 
gressively its  solubility  in  fats  and  hence  the  rate  of  diffusion 
into  living  cells. 

Having  shown  that  the  entrance  of  many  different  sub- 
stances into  cells  is  dependent  upon  their  solubility  in  fat- 
like bodies  we  may   ask  more  specifically,  What    are  these 


1  See  Hober:  1.  c,  p.  111. 


274  PHYSIOLOGY   OF  ALIMENTATION. 

substances  in  the  cell?  By  making  use  of  the  so-called 
"vital"  staining  methods,  that  is  through  use  of  stains  which 
will  color  living  protoplasm,  Overton  has  been  able  to  show 
that  these  fat-like  bodies — or  as  they  are  collectively  called, 
the  lipoids — are  cholesterin,  lecithin,  protagon,  and  cerebrin. 
These  substances  are  not,  of  course,  true  fats,  but  they  re- 
semble these  in  their  property  of  dissolving  more  or  less 
readily  the  compounds  which  were  found  above  to  enter 
living  cells.  The  conception  that  living  cells  are  surrounded 
by  lipoidal  membranes  seems,  therefore,  not  to  lack  experi- 
mental support,  and  osmotic  pressure  as  a  force  determining 
the  movement  of  dissolved  particles  and  of  water  becomes 
a  more  clearly  defined  force  in  phenomena  of  absorption  and 
secretion  when  this  selective  power  of  solution  of  the  surface 
films  of  cells  is  taken  into  consideration. 

It  must  not  be  thought,  of  course,  that  these  conceptions 
of  cell  membranes  and  the  movement  of  water  and  dissolved 
substances  through  them,  as  outlined  for  cells  in  general  and 
applicable  to  the  alimentary  mucosa  in  particular,  explain 
more  than  a  part  of  the  phenomena  of  absorption  and  secre- 
tion as  illustrated  by  the  gastro-intestinal  tract.  Even  in 
this  statement  we  are  not  considering  the  absorption  or 
secretion  of  substances  which  before  or  during  their  passage 
through  the  alimentary  mucosa  suffer  a  change,  such  as  the 
fats,  proteins,  and  carbohydrates.  All  this  will  become  more 
apparent  in  the  discussion  of  the  absorption  of  the  specific 
elements  of  our  food,  when  a  mass  of  isolated  facts  will  be 
found  that  still  lack  a  unifying  explanation. 

7.  The  Absorption  of  Salts.— Recognized  physical  laws  suf- 
fice at  present  to  explain  only  a  part  of  the  phenomena  ob- 
served in  the  absorption  from  the  gastro-intestinal  tract  of 
even  such  simple  substances  as  the  salts.  From  some  points 
of  view  the  absorptive  mucous  membrane  behaves  like  a  dead 
diffusion  membrane  on  one  side  of  which  there  is  found  the 
blood,  the  composition  of  which  may  be  looked  upon  as  fairly 
constant,  on  the  other  the  salt  solution  undergoing  absorption. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  275 

A  salt  solution  will,  in  the  course  of  time,  \>r  absorbed  by  the 
alimentary  tract  no  matter  whether  it  be  isotonic,  hypertonic, 
or  hypotonic  with  the  blood,  but  the  rule  differs  with  the 
different   kinds   of  salts.      Different   observers    agree    that 
when  a  hypertonic  solution  is  introduced  into  the  intestine 
its   volume   increases  at  first   through  a  diffusion  of  water 
into  it,  while  its  concentration  diminishes.      At  the  same 
time    certain    constituents     of    the    blood    diffuse    into    it. 
After  this  the  volume  of  solution  in  the  intestine  gradually 
diminishes.     These  phenomena  are  usually  explained  on  the 
basis  that  the  salt  diffuses  into  the  blood  because  its  concen- 
tration in  the  lumen  of  the  alimentary  tract  is  higher  than  the 
concentration  of  this  same  salt  in  the  blood,  while  various 
constituents  of  the  blood  diffuse  out  into  the  intestine  for 
the  same  reason.     The  initial  increase  in  the  volume  of  the 
solution  is  explained  in  those  cases  in  which  it  occurs  on  the 
basis  that  the  salt  under  consideration  does  not  diffuse  rapidly 
enough  not  to  allow  osmotic  differences  to  make  themselves 
felt    through  a  migration  of  water.     For  this  reason,  too,  it 
is  found    that  the  originally  hypertonic  solution  gradually 
approaches  isotonicity  with  the  blood. 

When  we  deal  with  the  diffusion  of  a  hypotonic  solution 
water  diffuses  into  the  blood  because  of  osmotic  differences, 
and  the  salt  solution  under  these  circumstances  also  ap- 
proaches isotonicity  with  the  blood.  When  this  occurs  the 
concentration  of  the  salt  in  the  solution  undergoing  absorp- 
tion is  increased  and  so  is  placed  in  a  position  to  diffuse  into 
the  blood,  but  this  lowers  the  osmotic  pressure  of  the  solu- 
tion in  the  lumen  of  the  intestine  once  more,  in  consequence 
of  which  water  is  again  absorbed  from  it  by  the  blood;  and 
so  these  processes  repeat  themselves  until  all  the  salt  solution 
is  absorbed. 

Solutions  isotonic  with  the  blood  arc  absorbed  quite  as 
easily  as  hypertonic  or  hypotonic  ones.  It  is  somewhat  dif- 
ficult to  see  what  forces  are  active  in  bringing  about  the 
transport  of  the  solution  into  the  blood.     The  explanation 


276  PHYSIOLOGY  OF  ALIMENTATION. 

ordinarily  given  is  as  follows:  While  the  inorganic  constitu- 
ents of  the  blood  may  diffuse  out  into  the  lumen  of  the  intes- 
tine, the  organic  constituents  (the  albumin,  globulin,  etc.), 
because  of  their  colloidal  nature,  are  practically  unable  to 
do  this.  While  colloids  exert  no  great  osmotic  pressure  they 
nevertheless  exert  some,  and  so,  even  after  all  other  osmotic 
differences  on  both  sides  of  the  diffusing  membrane  have  been 
equalized,  an  excess  of  osmotic  pressure  must  remain  on  the 
side  of  the  blood.  This  would  then  lead  to  the  abstraction  of 
a  small  amount  of  water  from  the  solution  in  the  intestine 
which  would  in  consequence  be  rendered  hypertonic.  Salts 
would  then  diffuse  into  the  blood,  then  more  water,  until, 
little  by  little,  the  whole  would  be  absorbed.1 

For  a  large  number  of  salts  the  rate  of  absorption  is  propor- 
tional to  the  velocity  of  their  diffusion  (Hober2).  In  the 
following  table  are  arranged  a  number  of  salts  in  the  order  of 
their  diffusion  velocities.  When  arranged  in  the  order  of  the 
velocity  with  which  these  salts  are  absorbed  from  isotonic 
solutions  when  equal  amounts  are  introduced  into  closed 
loops  of  intestine  the  grouping  remains  the  same. 

Sodium  chloride 

Sodium  nitrate 
Sodium  lactate 

Sodium  sulphate 

Sodium  malonate 

Sodium  succinate 

Sodium  tartrate 

Sodium  malate 

Magnesium  chloride 
Calcium  chloride 


1  More  detailed  discussion  of  these  still  unsatisfactory  theories  of 
absorption  cannot  be  entered  into  here.  See  Hober:  Physikalische 
Chemie  d.  Zelle  u.  d.  Gewebe,  Leipzig,  1902,  p.  184;  Pfluger's  Archiv, 
1898,  LXX,  p.  624.  Starling:  Journal  of  Physiology,  1896,  XIX,  p. 
313.     Kovesi:  Centralbl.  f.  Physiol.,  1897,  XI,  p.  553. 

2  Hober:  Pfluger's  Archiv,  1899,  LXXIV,  p.  246.  Zelle  una 
Gewebe,  Leipzig,  1902,  p.  190. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.   277 

Sodium  chloride  has,  of  all  these  salts,  the  greatest  diffusion 
velocity,  and  also  the  greatest  absorption  velocity.  From 
here  downwards  the  velocities  of  diffusion  and  of  absorption 
diminish  progressively.  In  the  same  unit  of  time  a  larger 
amount  of  the  solution  of  a  salt  in  the  first  group  will  dis- 
appear from  a  loop  of  intestine  than  of  an  isotonic  solution 
of  a  salt  contained  in  the  second  group,  and  this  will  dis- 
appear sooner  than  an  equal  amount  of  an  isotonic  solution 
of  a  salt  found  in  the  third  or  fourth  group.  For  all  salts  this 
does  not  hold,  however.  Of  the  halogen  salts  of  sodium,  for 
example,  which  have  all  the  same  diffusion  velocity,  the 
chloride  is  absorbed  most  rapidly,  then  the  bromide,  and 
finally  the  iodide.  All  fluorides  are  absorbed  exceedingly 
slowly,  as  also  the  carbonates,  due  no  doubt  to  secondary 
changes  produced  in  the  cells,  for  the  fluorides  are  proto- 
plasmic poisons,  and  the  carbonates  suffer  a  hydrolytic  disso- 
ciation  with  the  formation  of  free  OH  ions,  which  are  toxic 
in  even  very  low  concentrations. 

Hober  has  made  interesting  observations  on  the  paths  of 
absorption  of  the  salts.  From  studies  with  dyes  which  are  in 
part  soluble  in  the  lipoids  of  the  cells,  in  part  insoluble,  he 
has  been  able  to  show  that  salts  are  for  the  most  part  absorbed 
only  intercellularly;  that  is  to  say,  they  pass  into  the  blood 
not  through  the  epithelial  cells  of  the  absorbing  mucosa, 
but  through  the  intercellular  spaces.  If  solutions  of  the  salts 
of  various  dyes  soluble  in  the  lipoids  of  the  cell — such  as 
methylene  blue,  toluidin  blue,  or  neutral  red — are  introduced 
into  the  intestinal  tract  of  frogs,  microscopic  examination 
shows  that  the  dyes  affect  slightly  all  portions  of  the  ab- 
sorbing mucosa.  But  while  protoplasm,  nucleus,  and  intercel- 
lular substance  are  scarcely  colored,  granules  contained  within 
the  protoplasm  take  up  the  dyes  most  intensely.  The  granu- 
lar material  seems  to  be,  therefore,  an  excellent  solvent  for 
these  dves  and  probably  consists  of  those  substances  which 
are  collected  under  the  heading  lipoids.  Whim  solutions  of 
dyes  insoluble  in  the  lipoids— such  as  water-soluble  aniline 


278  PHYSIOLOGY  OF  ALIMENTATION. 

blue,  water-soluble  nigrosin;  or  benzoazurin — are  introduced 
into  the  intestine  the  urine  becomes  colored,  yet  no  deeply 
stained  granules  are  found  in  the  protoplasm. 

These  observations  only  show  that  the  intestinal  epithelium 
is  permeable  to  salts  soluble  in  the  lipoids;  it  does  not  as  yet 
prove  that  those  insoluble  in  the  lipoids  are  absorbed  only 
interepithelially.  But  this  is  rendered  probable  as  soon  as 
fixing  agents,  such  as  ammonium  molybdate,  osmic  acid, 
corrosive  sublimate,  picric  acid,  ammonium  picrate,  tannic 
acid,  or  gold  chloride,  are  used  to  fix  the  pictures  obtained 
after  simple  introduction  of  a  dye  into  the  intestinal  tract. 
Under  these  circumstances  it  is  found  that  if  the  fixing  agent 
is  one  soluble  in  the  lipoids  of  the  cell  (such  as  osmic  acid), 
the  granular  pigmentation  of  the  cell  found  after  the  use  of 
such  a  dye  as  methylene  blue  remains  unchanged.  If,  how- 
ever, a  fixing  agent  insoluble  in  the  cell  lipoids  (such  as  am- 
monium molybdate,  which  is  able  to  plasmolyze  cells)  is  used, 
the  blue  granules  in  the  cell  are  seen  to  dissolve,  to  move 
toward  the  periphery  of  the  cell  and  to  be  precipitated  here. 
This  is  because  the  ammonium  molybdate  remains  in  the 
intercellular  spaces  and  precipitates  the  dye  present  here. 
In  this  way  the  equilibrium  between  the  dye  without  and 
within  the  cells  is  destroyed.  The  stain  in  consequence  begins 
to  move  out  of  the  cell  toward  its  periphery,  where  it  meets  the 
ammonium  molybdate.  What  has  been  said  of  this  fixing 
agent  holds  for  every  one  of  the  fixing  agents  capable  of  re- 
acting with  the  stains  employed  and  not  soluble  in  the  lipoids. 
With  this  is  proven  quite  conclusively  that  salts  insoluble 
in  the  lipoids  make  their  way  from  the  intestine  into  the  blood 
only  through  the  interepithelial  spaces.1 

This  is,  perhaps,  the  best  place  to  touch  briefly  upon  the 
absorption  of  such  compounds  as  alcohol,  urea,  and  certain 

1  It  might  seem  from  this  that  the  ordinary  salts  are  entirely  in- 
capable of  entering  the  epithelial  cells  of  the  intestine  or  any  other 
cell  containing  lipoids.  This  is  not  true,  but  the  means  by  which 
they  may  or  do  enter  cannot  be  dealt  with  here. 


ALIMENTARY  TRACT   AS   A  A'    AliSolil'TlVL  SYSTEM.   279 

oilier  substances  which  are  absorbed  from  the  alimentary 
trad  much  more  rapidly  than  the  inorganic  salts.  While 
the  absorption  of  salts  from  the  stomach  is  still  questioned, 
the  rapidity  with  which  alcohol  disappears  from  the  gastric 
contents  is  truly  phenomenal.  Urea  also  is  much  more 
rapidly  absorbed  than  salts  of  a  simpler  composition.  The 
reason  for  this  is  at  once  apparent  when  we  assume  that 
while  the  inorganic  salts  can  pass  into  the  blood  only  through 
the  intercellular  spaces,  alcohol,  urea,  etc.,  are  soluble  in  the 
lipoids,  and  so  can  pass  directly  through  the  epithelial  cells 
as  wrell. 

From  what  has  been  said  it  seems,  therefore,  as  though  the 
behavior  of  the  epithelial  cells  of  the  gastro-intestinal  tract 
toward  certain  soluble  substances  is  not  unlike  the  behavior 
of  cells  in  general,  and  is  dependent  upon  the  same  powers  of 
selective  solution  by  their  surface  membranes. 

We  come  now,  however,  to  a  series  of  facts  for  which  an 
adequate  physical  explanation  is  entirely  lacking.  These 
facts  are  connected  with  the  predominant  'permeability  of  the 
gastro-intestinal  tract  in  one  direction.  While,  as  already  s ta  ted, 
some  of  the  constituents  of  the  blood  may  diffuse  into  a  solu- 
tion contained  in  the  lumen  of  the  intestine,  only  very  little 
passes  out  in  this  way.  Salts  found  in  the  blood  pass  only 
in  exceedingly  small  amounts,  if  at  all,  into  the  intestine, 
while  these  same  salts  in  various  concentrations  pass  easily 
from  the  alimentary  lumen  into  the  blood.  It  is  evident  that 
every  constituent  of  the  blood,  which,  like  the  albumin  and 
the  globulin,  is  unable  to  pass  into  the  intestine  can  in  this 
way  become  effective  in  absorbing  water,  and  in  consequence 
lead  to  a  passage  of  salt  from  the  fluid  in  the  alimentary  tract 
into  the  blood.  This  semi-permeability  of  the  absorbing 
mucosa  in  one  direction  only  would  therefore  greatly 
favor  the  absorption  of  substances  from  the  lumen  (Conx- 
beim). 

All  our  attempted  physical  explanations  of  absorption  by 
the  alimentary  mucosa  fail  when  v.e  approach  the  observa- 


280  PHYSIOLOGY  OF  ALIMENTATION. 

tions  of  Heidenhain,1  Reid,2  and  Cohnheim.  Heidenhain 
found  that  when  a  dog's  own  blood-serum  is  introduced  into 
its  intestinal  tract  it  is  absorbed.  Reid  removed  the  intestine 
from  rabbits  at  the  height  of  digestion  and  found  when  this 
is  cut  open  and  stretched  between  two  isotonic  sodium  chlo- 
ride solutions  that  the  salt  solution  is  pumped  from  the  side 
of  the  mucosa  toward  the  serosa.  Cohnheim  found  that  when 
the  alimentary  tract  is  removed  from  certain  marine  animals 
(Holothuria  tubulosa),  and  this  is  filled  with  10  to  30  c.c.  of 
sea-water,  and  the  whole  is  then  suspended  in  sea-water, 
that  this  moves  from  the  alimentary  tract  out  into  the  sur- 
rounding water.  In  all  these  experiments  we  have  no  dif- 
ferences in  osmotic  pressure,  and  at  present  we  cannot  say 
what  makes  the  liquids  move.  The  death  of  the  cells,  or 
certain  poisons  such  as  sodium  fluoride,  arsenic,  or  chloro- 
form, do  away  with  this  transport  of  serum,  sodium  chloride 
solution,  or  sea-water  from  the  side  of  the  mucous  mem- 
brane toward  the  serosa,  and  make  the  alimentary  wall  act 
like  an  ordinary  dead  diffusion  membrane.  But  it  explains 
nothing,  of  course,  when  we  say  that  such  a  transport  is 
dependent  upon  the  living  activity  of  the  cells. 

The  predominant  permeability  of  the  intestinal  tract  in 
one  direction  can  be  markedly  influenced  experimentally. 
When  a  dextrose  solution  is  introduced  into  a  loop  of  small 
intestine,  it  is  absorbed.  According  to  experiments  carried 
out  by  Gertrude  Moore  and  myself  this  same  glucose  solu- 
tion when  injected  into  the  blood  is  not  excreted  into  the 
lumen  of  the  intestine.  This  happens,  however,  as  soon  as 
certain  salts  (such  as  sodium  chloride)  are  injected  along 
with  the  sugar  solution,  presumably  because  these  salts 
modify  this  predominant  permeability  in  one  direction.  The 
intestine  in  consequence  now  excretes  a  substance  which  it 


1  Heidenhain:  Pfluger's  Archiv,  1894,  LVI,  p.  579. 
?Reid:  Phil.  Trans.  Royal  Soc,  1900,  CXCII,  p.  231.     Journal  of 
Physiol.,  1601,  XXVI,  p.  436. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  2S1 

absorbed  formerly.  What  has  been  said  of  dextrose  holds 
also  for  a  number  of  other  substances. 

The  different  portions  of  the  alimentary  tract  absorb  salts 
in  very  different  amounts.  Under  ordinary  circumstances 
the  amount  of  salt  absorbed  in  the  mouth  or  oesophagus  is 
to  be  looked  upon  as  practically  nothing.  While  certain  au- 
thors believe  that  considerable  amounts  of  salt  are  absorbed 
in  the  stomach,  others  question  it  entirely.  The  small  in- 
testine absorbs  salts  freely  throughout  its  entire  length, 
though  the  jejunun  seems  to  be  somewhat  more  active  in  this 
regard  than  the  ileum.  The  large  intestine  also  takes  up  salts, 
but  not  to  the  same  extent  as  the  small  bowel. 

Under  certain  circumstances  one  region  of  the  alimentary 
tract  may  absorb  a  salt  while  another  is  excreting  this  same 
salt.  One  and  the  same  portion  of  the  intestine  may  even 
absorb  a  salt  which  under  somewhat  different  conditions  it 
excretes.  The  character  of  the  changes  which  take  place 
in  the  absorbing  structure  of  the  alimentary  tract  to  render 
such  phenomena  possible  are  not  as  yet  understood,  and  the 
visible  alterations  (swelling,  contraction,  coagulation)  often 
observed  in  the  absorbing  surfaces  still  lack  a  unifying 
physical  explanation. 


CHAPTER  XVI. 

THE  ALIMENTARY  TRACT  AS  AN   ABSORPTIVE   SYSTEM 

{Continued). 

8.  The  Absorption  of  Carbohydrates. — The  carbohydrates 
which  are  of  chief  importance  in  the  physiology  of  alimenta- 
tion in  so  far  as  they  are  found  in  any  ordinary  mixed  meal, 
"4r  are  the  polysaccharides  starch,  glycogen,  and  cellulose,  the 
it    disaccharides-  cane-sugar,   malt-sugar,  and   milk-sugar,  and 
f  |    fjie   monosaccharides  dextrose.  IsRvulose.  and  galactose.     Of 
the  polysaccharides  the  starches  make  up  not  only  the  bulk 
of  this  class  of  food,  but  of  all  the  carbohydrates  that  are 
enjoyed  in  an  ordinary  diet.     The  consumption  by  an  ordi- 
nary individual  of  several  hundred  grams  of  starch  a  day  in 
the  form  of  bread,  potatoes,  beans,  etc.,  is  not  uncommon. 
A  few  grams  of  glycogen  enter  into  the  ordinary  daily  diet  as 
constituents  of  lean  meat,  liver,  etc.     Cellulose  is  obtained 
through  the  vegetable  constituents  of  the  diet,  more  particu- 
larly celery,  string  beans,  turnips,  carrots,  beets,  etc. 

Sucrose  (cane-  or  beet-sugar)  as  the  ordinary  sugar  of  com- 
merce and  the  recognized  sweetening  agent  of  our  food  makes 
up  the  bulk  of  the  disaccharides  which  we  consume,  though 
the  exact  amount  consumed  in  a  day  is  subject  to  the  widest 
individual  variations.  Malt-sugar  is  obtained  in  small 
amounts  through  beverages  and  "breakfast  foods,"  into  the 
composition  of  which  sprouted  grains  enter.  Milk-sugar 
comes  to  us  through  milk  and  certain  of  its  derivatives;  only 
rarely  as  a  distinct  addition  to  an  ordinary  mixed  diet. 
Dextrose  and  laevulose  are  found  in  certain  fresh  and  dried 

282 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  283 

fruits,  and  in  the  commercial  "glucoses"  (corn-sugar,  molas- 
ses, etc.)-  The  dextrose  ;hm1  la-vnlose  found  in  the  alimentary 
fr-wi  ja  derived  with  the  exceptions  indic-i led,  from  the  de- 
ipositioTi  of  the  polysaccharides  :ind  disaccharides  of  the 

udiet.  Galactose  enters  as  such  into  the  diet  practically  nol  al 

all.    11  is  pfodjififid  in  the  alimentary  tract   thron.fh  Hie  actio^ 

,of  lada.se  upon  it |  j  1 1-  -.-<n<--.-i  t  Either  directly  or  indirect  ly.d^x^ 
Jaxise_Jpecomes  the  predominating  sugar  of  the  alimentary 
tract.  Not  only  does  it  constitute  the  bulk  of  the  com- 
mercial "glucose,"  but  it  appears  as  the  ultimate  product  of 
the  decomposition  of  every  polysaccharide  and  disaccharide. 
Glycogen  is  split  directly  into  dextrose  through  amylase.  The 
same  ferment  converts  starch  into  maltose,  which  through 
maltase  is  converted  into  dextrose.  Dextrose  appears  as  one- 
half  of  the  product  of  the  action  of  sucrase  on  sucrose,  and 
lactase  on  lactose.  Cellulose,  though  acted  upon  only  by  the 
bacterial  enzymes  of  the  alimentary  tract,  yields  dextrose 
when  this  occurs. 

We  have  to  ask  now  in  what  form  the  carbohydrates  of 
the  diet  are  absorbed.  There  seems  to  be  little  doubt  that 
the  monosaccharidesjiro  absorbed  as  such.  With  the  disac- 
charides  matters  are  somewhat  different.  If  sucrose,  maltose, 
or  lactose  are  fed  slowly,  they  are  all  converted  into  mono- 
saccharides before  they  are  absorbed.  When,  however,  those 
disaccharides  are,  fed  rabidly,,  then  they  are  not  all  split 
before  they  are  aosorbed,  ana  sucrose,  maltose,  and  lactose 
may  be  recovered  as  such  from  the  blood  and  from  the  urine, 
for  these  disaccharides  when  present  in  the  circulating  blood 
in  a  concentration  exceeding  a  very  small  fraction  of  a  per- 
cent are  eliminated  through  the  kidneys.  Ordinarily  it  is 
said  that  the  disaccharides  appear  in  the  blood  and  the  urine 
if  they  are  fed  in  too  large  amounts.  This  is  nol  the  essential 
factor,  however,  but  the  time  taken  in  feeding  the  amount, 
for  if  the  sugar  solution  is  not  absorbed  too  rapidly  it  does 
not  pass  over  into  t he  blood  in  an  unchanged  state. 

Starch,  glycogen,  and  cellulose  all  being  colloidal  bodies  arc 


284  PHYSIOLOGY  OF  ALIMENTATION. 

unable  as  such  to  pass  through  the  walls  of  the  alimentary 
tract.  They  must  be  acted  upon  by  the  enzymes  found 
here  before  they  can  be  absorbed.  The  starch  may  be  ab- 
sorbed as  soon  as  it  has  been  broken  down  to  the  maltose 
stage,  but  most  of  it  seems  to  be  absorbed  in  the  form  of 
dextrose.  The  glycogen  is  readily  converted  into  dextrose 
and  is  as  rapidly  absorbed.  The  cellulose  of  the  food  is 
ordinarily  classed  as  a  substance  which  is  of  no  use  from  a 
nutritional  standpoint,  for  it  cannot  be  absorbed  as  such 
and  no  enzymes  are  secreted  by  the  alimentary  tract  which 
can  act  upon  it.  Only  the  cellulose-splitting  ferment  (cytase) 
contained  in  certain  of  the  bacteria  found  in  the  alimentary 
tract  is  able  to  convert  cellulose  into  sugar,  and  experiment 
shows  that  the  amount  produced  in  this  way  is  exceedingly 
small. 

Of  great  interest  from  a  medical  standpoint  are  the  ex- 
periments of  Hofmeister,1  who  has  determined  the  "assimila-. 
t[nn  limijallof  various  carbohydrates.  By  the  assimilation 
limit  (which  is  not  a  well-chosen  term)  Hofmeister  under- 
stands the  amount  of  a  sugar  that  may  be  administered  to  an 
animal  without  the  appearance  of  sugar  in  any  form  in  the 
urine.  It  is  clear  that  a  large  number  of  factors  play  a  role 
in  this  complicated  picture,  and  it  is  not  strange  that  the 
figures  obtained  should  vary  widely  from  each  other.  Never- 
theless the  general  conclusions  which  may  be  drawn  are 
clear  enough  and  are  valuable  in  any  dietary  scheme  in  which 
the  quality  and  quantity  of  carbohydrates  administered  plays 
f  a  role.  It  has  been  found  that  the  assimilation  limit  of  any 
sugar  is  different  not  only  in  different  animals,  but  varies  in 
one  and  the  same  animal  under  different  physiological  con- 
ditions, such  as  the  rapidity  with  which  absorption  takes 
^  place,  the  amount  of  sugar  already  present  in  the  blood,  and 
the  nutritional  state  of  the  animal  as  a  whole.  A  dog  that  has 
been  starved  for  a  number  of  days  will  excrete  sugar  in  the 

1  Hofmeister:    Arch.  f.  exp.  Path.  u.  Pharm.,  1889,  XXV,  p.  240, 
and  1890,  XXVI,  p.  350. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.    285 

urine  after  being  fed  10  to  l.">  grams  of  starch  paste,  while  a 
healthy  dog  will  stand  several  times  this  amount  at  a  single 
feeding  and  not  excrete  sugar.1  Most  striking  is  the  assimi- 
lation limit  of  one  and  the  same  animal  for  different  kinds  of 
carbohydrates.  -jOnlmary  starch  Uadi  '-11  the  lll1"1!^  in  t|ic 
amount  that  may  he  consumed  in  twenty-four  hours  (mori- 
than  500  grains)  without  the  appearance  of  sugar  in  the 
urine.  Next  in  order  stand  dextrose,  lsevulose,  sucrose,  mal- 
tose, and  lactose  in  the  order  named.  The  reason  why  the 
disaccharides  stand  lowest  is  no  doubt  to  be  sought  in  the 
fact  that  when  these  are  fed  rapidly  and  in  large  amounts, 
they  pass  without  change  into  the  blood, ^a^^s^r^eJiGj^yr 
and  muscles  retain  the  disaccharides  but  imperfectly,  their 
concentration  in  the  blood  soon  exceeds  the  limits  at  which 
the  sugar  passes  over  into  the  urine. 

The  rapidity  with  which  the  different  sugars  are  absorbed 
seems  not  qt,  all  dependent  rp"^  tbfiM  nTP<a  of  diffusion  or 
differences  in  osmotic  pressure  The  subject  has  been  investi- 
gated by  Albertoni,2  Rohmaxn  and  Nagano.3  Sugars  are 
absorbed  not  only  from  solutions  which  are  hypertonic  or  iso- 
tonic with  the  blood  but  also  such  as  are  hypotonic.  When 
isosmotic  solutions  of  sugars  are  compared  it  is  found  that  dex- 
trose is  a_hsorberj  most  rapidly,  sucrose  next,  and  much  more  . 
slowly  lactose.  But  the  amount  absorbed  in  any  unit  of  time 
varies,  much  more  of  any  given  sugar  being  absorbed  in  the 
first  hour  after  feeding  than  in  subsequent  hours.  Starch, 
as  already  pointed  out,  cannot  be  absorbed  as  such.  Its 
absorption  is  dependent  upon  the  velocity  with  which  it  is 
split  into  absorbable  sugars.  These  sugars  .amder  normal 
circumstances  are  absorbed  as  rapidly  as  formed.  Since  the 
amount  of  amylolytic  change  is  greatest  not  immediately 
after  eating  but  in  the  second  or  third  hour  of  the  digestive 

1  My  own  attempts  to   repeal    this  experiment  succeeded  only  once 
on  one  out  of  four  dogs. 

2  Albbhtoni:  Centralbl.  f.  Physiol.,  1901,  XV,  p.  157. 

3  Rohmanx  and  Nagano:  Centralbl.  f.  Phywol.,  1901,  XV,  p.  494. 


i 


286  PHYSIOLOGY  OF  ALIMENTATION. 

period,  ^  j«  fomj  that  siaseh  i-q  n1gn  mast  rapidly,  absorbed 

during    this    ppriogV 

After  what  has  been  said  it  becomes  somewhat  difficult 
to  explain  the  fate  of  starches  which  under  experimental 
conditions  may  be  fed  an  animal  in  which  the  salivary  and 
pancreatic  secretions  are  lacking,  or  patients  in  whom  these 
are  insufficient  in  amount  or  poor  in  the  proper  enzymes. 
It  has  been  found  that  in  dogs  in  which  the  pancreatic  ducts 
rhave  beep  ligaiad  thai  upwards  of  50  pprppnt,  of  thp  starches 
fed  cannot  be  recovered  from  the  faeces.  By  what  agencies 
these  starches  are  rendered  absorbable  is  not  known,  for  the 
action  of  the  gastric  acid,  the  bacteria  of  the  alimentary  tract, 
and  the  slight  amylolytic  activity  attributed  by  some  to  the 
intestinal  juice  seem  insufficient.1 

The  question  of  the  channels  through  which  the  carbo- 
hydrates are  distributed  to  the  body  after  passing  through 
the  epithelium  of  the  alimentary  tract  seems  to  be  settled 
beyond  question,    v.  Mering  showed  in  1877  that  the  absorbed 
carbohydrates  pass  through  the  portal  vpin,  *r>  fhp  r"rej   for 
while  under  normal  conditions  the  blood  of  this  vessel  con- 
tains  no  more   than   about    0.2  percent    dextrose,   it   may 
contain  twice  this  amount  after^r  carbohydrate  meal.     De- 
t  terminations  of  the  sugar  content  of  the  lymph  obtained  from 
I    the  thoracic  duct  showed  that  this  fluid  contained,  both  before 
\   and  after  a  meal  of  carbohydrates,  a  fa.irTvp.onsta.nt,  pprppnt. 
*  (less  than  0.2   percent)    of   sugar.     T>"«  shows  that  nn,oW 
ordinary    circumstances    all  the    ca,rbohvdra.tps  of  thp  food  , 
leave  the  alimentary  tract  by  wav  of  thp  blood.     When, 
however,    excessive    amounts    of    carbohydrates    are    fed   a 
small  portion  of  them  may  ■  pass  over  into  the  lymph-chan- 
nels,  as_  shown  by  Ginsberg's  observations  on  rabbits  and 
dogs.    Munk  and  Rosenstein's  studies  on  a  case  of  lymphatic 
fistula  in  a  human  being  fully  confirm  these  observations. 
It  was  found  in  this  case,  in  which  practically  all  the  lymph 

1  See  Munk:  Ergebnisse  d.  PhysioT.,  1902, 1,  lte  Abth.,  p.  308. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.  287 

coming  from  the  intestines  was  secreted  externally,  that 
less  than  V-'  gram  of  sugar  was  excreted  through  this  channel 
after  a  feeding  <>[  ]()()  grams  Ol  BJflJCfih  ■'"1'1  M'";-'r  in  Other 
words,  not  even  1  percent  of  the  absorbed  carbohydrates.1 

9.  The  Absorption  of  Fat.— The  means  by  which  the 
often  enormous  quantities  of  fat — 100  to  200  grams  daily — 
which  the  human  being  consumes  are  absorbed  has  for  more 
than  half  a  century  been  the  subject  of  most  active  research 
and  discussion.  It  is  clear  that  in  the  fat  of  our  food  we  ha  vo 
a  substance  which  is,  practically  speaking,  insoluble  in  \v:iter 
and  but  little  more  soluble  in  protoplasm.  In  discussing 
the  problem  of  fat  absorption  we  must,  therefore,  ask  first 
of  all,  Can  fat  be  absorbed  as  such  or  is  it  first  changed  into  a 
soluble  form? 

Those  authors  who  have  held  to  the  idea  that  fat  is  ab- 
sorbed as  fat  have  called  attention  to  the  fact  that  even 
though  it  is  insoluble,  fat  can  be  very  finely  divided  and  kept 
suspended  in  water  in  a  so-called  emulsion.  Not  only  do 
many  fats  enter  the  alimentary  tract  in  the  form  of  such  an 
emulsion — for  example,  milk  and  raw  yolk  of  eggs — but  a 
number  of  agents  exist  in  the  body  which  have  the  power  of 
emulsifying  fats  to  a  very  high  degree.  As  of  first  impor- 
tance in  this  direction  we  must  mention  the  bile,  under  the 
influence  of  which  any  of  the  ordinary  fats  of  the  diet,  such  as 
butter,  the  fat  of  meat,  and  olive-oil,  may  be  speedily  emulsi- 
fied. 

While  these  agents  exist  which  can  alter  so  markedly  the 
physkal  state  of  the  fats,  there  are  others  which  are  equally 
potent  in  bringing  about  a  chemical  change  in  them.  Of 
first  importance  in  this  direction  is  lipase,  a  widely  distributed 
ferment  which  has  the  power  of  splitting  fats  into  fatty  acid 
and  alcohol.  This  chemical  change  which  fats  may  suffer 
in  the  body  affects  markedly  the  question  of  fal  absorption, 
for  these  products  of  fa  I   digestion  are  many  of  them  soluble 

1  See  Mink:  Ergebniss  -  d.  Physiol.,  1902, 1.  Lte  Abth.,  p.  309,  where 

references  to  the  literature  will  U-  found. 


288  PHYSIOLOGY  OF  ALIMENTATION. 

in  water.  Others  are  soluble  in  water  if  bile  is  present,  and 
some  are  soluble  in  protoplasm.  If,  therefore,  it  could  be 
shown  that  under  the  conditions  which  exist  in  the  body  it 
is  possible  for  all  the  fat  of  a  fatty  meal  to  be  converted  into 
digestion  products  soluble  in  the  body  fluids,  and  this  within 
the  time  allowed  for  the  absorption  of  such  a  meal  under 
physiological  conditions,  one  of  the  great  difficulties  in  the 
way  of  believing  that  all  fat  is  absorbed  only  in  the  form  of 
its  soluble  digestion  products  would  be  overcome.  The  ex- 
tent to  which  the  fat  of  a  fatty  meal  is  split  into  fatty  acid  and 
alcohol  during  an  ordinary  period  of  digestion  has  been  greatly 
underrated  by  the  majority  of  investigators.  We  know  now 
from  the  observations  of  Rachford  x  that  in  the  hours  making 
up  the  ordinary  period  of  pancreatic  activity  consequent 
upon  a  meal  ample  time  is  allowed  for  the  splitting  of  at 
least  the  larger  portion,  and  probably  all  of  the  fat  consumed 
in  that  meal. 

Before  entering  further  into  the  discussion  of  this  question 
let  us  ask  first  of  all  whether  fat  can  be  absorbed  in  the  form 
of  an  emulsion.  If  this  question  is  answered  in  the  affirma- 
tive, then  we  have  to  ask,  Is  all  the  fat  absorbed  in  this  form, 
or  only  a  part  of  it,  and  how  much?  The  mere  question  as 
to  whether  fat  can  be  absorbed  in  the  form  of  an  emulsion 
must,  perhaps,  be  answered  in  the  affirmative.  From  a 
physical  standpoint  the  question  is  one  which  asks  whether 
substances  having  a  high  molecular  weight  can  diffuse  through 
animal  membranes.  The  physical  experiment  to  settle  this 
question  has  been  made  by  Eijkmann,2  who  found  that  a 
solution  of  glue  poured  upon  an  agar-agar  plate  will,  if  a 
proper  temperature  be  maintained,  soon  diffuse  into  the 
agar-agar.  In  this  case  we  have  one  colloid  diffusing  into 
another.  The  physiological  experiment  to  answer  this  ques- 
tion has  been  made  by  Friedenthal,3  who  fed  colloidal  so- 

1  Rachford:  Journal  of  Physiology,  1891,  XII,  p.  72. 

2  Eijkmann:  Centralbl.  f.  Bacterid.,  1901,  XXIX,  p.  841. 

3  Friedenthal:  Archiv  fur  (Anat.  und)  Physiologie,  1902,  p.  149. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.     2R9 

dium  silicate  to  rabbits  and  young  dogs  and  was  able  to  re- 
cover the  salt  from  the  urine1  in  exceedingly  small  but  never- 
theless distinct  amounts.  This  means,  of  course,  that  the 
colloidal  sodium  silicate  diffused  through  the  gastro-intestinal 
wall. 

There  is  a  difference,  however,  between  asking  whether  fat 
can  pass  as  such  through  the  intestinal  mucous  membrane 
and  whether  under  ordinary  circumstances  this  is  the  way 
in  which  it  is  absorbed.  There  seems  to  be  little  doubt  that 
even  if  fat  can  be  absorbed  as  such,  most  of  it  passes  through 
the  intestinal  wall  (and  from  tissue  to  tissue)  in  the  form  of 
its  soluble  digestion  products.  As  evidence  of  this  we  may 
quote  the  experiments  of  Connstein.1  If  the  essential  change 
necessary  for  the  absorption  of  fats  lay  in  their  conversion 
into  an  emulsion  in  the  animal  body,  then  it  would  be  reason- 
able to  expect  that  a  fine  emulsion  of  one  fat  should  be 
absorbed  as  rapidly  as  an  emulsion  of  any  other  fat  provided 
it  were  equally  finely  divided.  An  emulsion  of  lanolin  ought, 
therefore,  to  be  absorbed  as  readily  as  an  emulsion  of  butter- 
fat.  As  an  actual  matter  of  fact,  Connstein  found  that  when 
he  fed  a  dog  with  a  lanolin  emulsion  in  water  97 \  percent  of 
the  entire  amount  fed  could  be  recovered  from  the  faeces. 
The  formation  of  an  emulsion  from  the  fat  is,  therefore,  only 
of  secondary  importance  in  the  absorption  of  this  foodstuff. 
The  real  reason  why  lanolin  is  not  absorbed  in  the  above  ex- 
periment lies  in  the  fact  that  it  is  acted  upon  only  exceedingly 
slowly  by  the  fat-splitting  enzymes  of  the  digestive  tract, 
and  hence  is  not  converted  into  the  absorbable  products  of 
fat  digestion. 

The  recognition  by  Kastle  and  Loevexiiart,  and  inde- 
pendently of  them  by  Hanriot,  that  the  action  of  lipase  is  re- 
versible, has  altered  entirely  our  conception  of  the  mechanism 
by  which  fat  is  absorbed  from  the  intestinal  tract.'-'    Tin1  belief 

'Connstein:  Arcliiv  fur  (Anaf.  u.)  Physiol.,  ISO1.),  p.  'M). 
2  See  p.  151,  and  Loevenhaht:  American  Journal  of  Physiology,  1902, 
VI,  p.  332, 


290  PHYSIOLOGY  OF  ALIMENTATION. 

of  the  older  observers  that  fat  is  absorbed  chiefly  in  the  form 
of  an  emulsion  was  based  upon  physiological  experiments 
and  histological  studies  which  showed  that  in  ordinary  diges- 
tion the  fat  of  the  food  is  emulsified  in. the  lumen  of  the  gut, 
appears  as  droplets  in  the  cells  lining  the  gut,  and  in  the  same 
form  in  the  chyle,  the  fat-laden  lymph  which  leaves  the  in- 
testinal tract  after  a  fatty  meal.  This  conception  was  further 
strengthened  by  the  analytical  results  of  physiological  chem- 
ists, who  found  but  little  fatty  acid  and  alcohol  (glycerine)  in 
any  of  these  localities.  The  idea,  therefore,  that  fat  was  ab- 
sorbed in  any  other  form  than  fat  received  little  support,  and 
the  formation  of  fatty  acid  and  alcohol  during  digestion  was 
looked  upon  as  of  little  importance. 

As  the  following  will  show,  fat  is  in  all  probability  absorbed 
only  after  it  has  first  been  split  into  fatty  acid  and  alcohol 
and  never  in  the  form  of  the  original  foodstuff.  The  observa- 
tions of  Rachford  and  the  recognition  of  the  reversible 
action  of  lipase  suffice  entirely  to  explain  the  facts  cited 
above  which  have  so  long  been  quoted  in  support  of  the  older 
ideas  of  fat  absorption. 

Under  normal  circumstances  fat  is  absorbed  with  great 
rapidity  from  the  intestinal  lumen.  From  a  physico-chemical 
standpoint  alone,  therefore,  it  appears  very  unlikely  that  fat 
enters  the  cells  of  the  intestinal  mucosa  as  such,  for  fat  has 
only  slight  powers  of  diffusion,  especially  into  solvents  made 
up  chiefly  of  water,  such  as  protoplasm.  To  overcome  this 
argument  the  intestinal  epithelium  has  been  endowed  with 
powers  of  amoeboid  motion  and  (hypothetical)  tubules  sur- 
rounded by  contractile  protoplasm.  Even  were  its  entrance 
into  the  intestinal  mucosa  explained  in  this  way,  its  exit  into 
the  lacteals  and  from  here  into  the  various  tissues  of  the  body 
would  yet  have  to  be  accounted  for.  The  same  explanation 
could  evidently  not  hold  in  all  these  cases  of  absorption.  The 
belief,  on  the  other  hand,  that  fat  enters  and  leaves  the  intesti- 
nal mucosa  only  in  the  form  of  its  cleavage  products — in  fact, 
enters  and  leaves  all  tissues  in  this  form — meets  with  no  such 


ALIMENTARY  TRACT  AS  AN  ABSORPTH  E  SYSTEM.    291 

objections.  The  cleavage  products  of  Eat  are  readily  soluble 
in  the  fluids  and  tissues  of  the  body  and  diffuse  with  great 
rapidity. 

The  exact  form  in  which  the  cleavage  products  are  absorbed 
cannot  as  yet  be  looked  upon  as  settled  definitely.  For  the 
sake  of  simplicity  we  will  adopt  Munk  and  Loevenhaht's 
opinion  that  fat  is  absorbed  as  fatty  acid  and  alcohol.  This 
is  probably  correct,  though  it  is  at  variance  with  the  belief 
of  certain  other  investigators  that  the  fatty  acid  unites  with 
the  alkalies  of  the  body  and  forms  soaps.  Whichever  may 
ultimately  have  to  be  adopted  will  not  alter  the  fundamental 
principles  of  the  mechanism  of  fat  absorption.  Since  certain 
of  the  fatty  acids  are  practically  insoluble  in  water,  and 
since  solubility  is  so  important  a  factor  in  absorption,  it  is 
well  to  bear  in  mind  Moore  and  Rockwood's  experiments, 
which  show  that  the  insoluble  fatty  acids  become  freely  soluble 
in  the  presence  of  bile. 

It  is  well  to  impress  anew  upon  the  reader  that  lipase, 
which  we  ordinarily  think  of  as  a  constituent  of  the  pan- 
creas and  the  pancreatic  juice  only,  is  really  very  widely 
distributed  throughout  the  body,  where  it  occurs  in  different 
amounts  in  practically  every  tissue  and  fluid.  Of  immediate 
interest  to  us  is  the  fact  that  lipase  occurs  in  the  mucosa  of 
the  intestine  as  also  in  the  lymphatic  glands,  lymph,  and  the 
blood. 

Bearing  in  mind  the  facts  stated  above  regarding  lipase, 
its  action  and  its  distribution,  let  us  trace  the  chemical  changes 
which  follow  the  ingestion  of  a  fat.  This  substance  is  not 
acted  upon  in  the  mouth  or  oesophagus.  As  lipase  is  found 
in  the  gastric  juice  and  gastric  mucosa  it  is  possible  that 
some  digestion  may  occur  in  this  viscus.  This  will  occur 
especially  if  the  meal  has  been  one  which  calls  forth  a  secre- 
tion of  but  little  hydrochloric  acid  or  if  the  digestion  occurs 
in  a  stomach  which  through  pathological  change  is  secreting 
a  deficient  amount  of  this  acid.  The  activity  of  the  lipase 
under   these    circumstances   is   not    interfered   with.     It  is 


292  PHYSIOLOGY  OF  ALIMENTATION 

entirely  possible  that  the  appearance  of  butyric  and  other 
fatty  acids  in  diseases  of  the  stomach  is  attributable  in  part 
at  least  to  the  activity  of  the  lipase  normally  present  here. 

But  even  if  under  normal  circumstances  little  or  no  diges- 
tion of  fats  occurs  in  the  stomach,  active  digestion  of  this 
food  begins  as  soon  as  the  gastric  contents  are  neutralized 
in  the  duodenum  and  have  poured  out  upon  them  the  pan- 
creatic juice  and  the  bile.  The  function  of  the  latter  we  will 
ignore  for  the  present.  Let  us  ask  first  of  all  how  much  of 
the  fat  will  be  split  under  the  influence  of  the  pancreatic  juice 
as  the  mixture  of  the  two  moves  down  the  intestine.  It  is 
clear  that  if  the  intestine  were  replaced  by  a  glass  tube,  by 
no  means  all  of  the  fat  would  be  split,  but  only  a  portion  of 
it,  or  to  put  it  more  technically,  fat  would  undergo  cleavage 
until  an  equilibrium  had  been  established  between  this  sub- 
stance on  the  one  hand  and  fatty  acid  and  alcohol  on  the 
other.  In  other  words,  we  recognize  here  again  an  equa- 
tion similar  to  the  one  given  on  page  107: 

Fat  ±±  Fatty  acid  +  Alcohol. 

In  the  animal  body  conditions  are  somewhat  different  than 
in  a  glass  tube.  While  in  a  glass  tube  the  products  of  the 
cleavage  accumulate,  this  does  not  occur  in  the  intestine,  for 
here  the  fatty  acid  and  alcohol  diffuse  into  the  intestinal 
mucosa  as  soon  as  formed.  Evidently,  therefore,  the  state 
of  equilibrium  outlined  above  never  comes  to  pass  in  the  in- 
testine, and  the  cleavage  of  the  fat  continues  until  all  has 
been  split,  in  other  words,  all  has  been  absorbed.  This  really 
occurs,  for  under  normal  circumstances  no  fat,  or  practically 
none,  is  found  in  the  faeces. 

Let  us  see  now  what  becomes  of  the  fatty  acid  and  alcohol 
which  have  diffused  into  the  lining  cells  of  the  intestine.  At 
the  beginning  of  a  meal  these  cells  contain  no  fat,  but  they 
do  contain  lipase.  As  the  fatty  acid  and  alcohol  diffuse 
into  them  evidently  the  reverse  of  what  occurred  in  the  lumen 


ALIMENTARY  TRACT  A3  AN  ABSORPTIVE  SYSTEM.      293 

of  the  gut  must  happen  here,  for  since  the  action  of  lipase 
is  reversible  it  must  synthesize  fat  from  the  products  of  the 
fat  digestion  which  is  going  on  in  the  lumen  of  the  intestine. 
In  other  words, 

Fatty  acid  +  Alcohol  <=±  Fat. 

It  is  this  synthesis  of  fat  in  the  epithelium  of  the  gut  which 
gives  rise  to  the  appearance  of  fat  droplets  in  this  locality, 
and  which  the  older  observers  looked  upon  as  evidence  sup- 
porting the  idea  that  fat  is  absorbed  as  an  emulsion. 

We  have  yet  to  explain  the  transport  of  the  fat  into  the 
lymph-channels.  The  fatty  acid  and  alcohol  which  diffuse 
into  the  cells  lining  the  intestine  do  not  stop  here  but  pass 
on  into  the  lymph  current  beyond.  At  the  beginning  of  a 
digestion  period  this  is  also  free  from  fat,  but  it  contains  lipase. 
Evidently  the  same  play  must  occur  in  this  liquid  tissue  which 
we  saw  take  place  in  the  cells  lining  the  intestine.  Under 
the  influence  of  the  lipase  the  fatty  acid  and  alcohol  are  syn- 
thesized into  fat,  and  it  is  this  fat  which  evidences  itself  in 
the  droplets  found  in  the  lymph  returning  from  the  intestine. 
That  we  are  dealing  with  a  chemical  equilibrium  in  this  case 
also  is  shown  by  the  fact  that  the  lymph  always  shows  the 
presence  of  free  fatty  acid  accompanying  the  fat. 

In  order  to  get  a  conception  of  the  process  of  fat  absorp- 
tion as  a  whole,  we  need  only  to  imagine  these  different  proc- 
esses of  analysis,  diffusion,  and  synthesis  going  on  simul- 
taneously and  side  by  side.  We  are  in  a  position  now  to  rec- 
ognize the  unimportant  role  played  by  the  fat  droplets  which 
appear  in  the  epithelial  cells  of  the  intestine.  They  are 
evidently  transitory  creations,  which  exist  only  as  long  as 
fatty  acid  and  alcohol  are  diffusing  through  these  cells.  When 
the  last  remnants  of  fatty  acid  and  alcohol  diffuse  out  of  the 
cells  into  the  lymph  stream  (ho  fat  in  the  cells  can  no  longer 
maintain  itself,  and  the  lipase  which  before  hastened  its 
synthesis  now  hastens  its  analysis  until  i!  too  has  disappeared 
as  fatty  acid  and  alcohol  into  the  lymph  stream.     This  leaves 


294  PHYSIOLOGY   OF  ALIMENTATION. 

the  cells  once  more  in  the  empty  condition  in  which  they 
were  found  at  the  beginning  of  the  digestion  period. 

Under  the  influence  of  the  lipase  they  contain,  the  tissues 
of  the  body  also  store  fat  when  it  is  plentiful  in  the  food  and 
give  it  up  during  starvation  in  the  same  manner  as  the  epithe- 
lial cells  of  the  intestinal  mucosa ;  but  a  discussion  of  this 
problem  is  beyond  the  limits  of  our  subject.  One  more  fact 
is  of  interest  in  support  of  the  ideas  of  fat  absorption  ad- 
vanced above.  We  would  expect  from  chemical  considera- 
tions alone  that  if  a  certain  fat  is  digested  by  lipase,  the 
products  of  its  digestion  should,  when  synthesized  under  the 
influence  of  the  same  ferment,  yield  the  original  fat,  and 
that  this  ought  to  hold  when  different  kinds  of  fat  are  con- 
sumed by  animals.  Not  only  were  Munk  and  Rosenstein 
able  to  isolate  from  the  lymph  obtained  from  their  patient 
with  a  lymphatic  fistula  an  oily  fat  when  olive-oil  was  fed, 
and  a  tallow-like  fat  when  mutton-tallow  was  administered, 
but  Rosenfeld  x  has  been  able  to  show  niore  recently  that  if 
one  dog  is  fed  cocoa-butter  and  another  mutton-tallow  the 
fats  deposited  in  each  case  correspond  to  those  ingested. 
Goldfish  and  carp,  moreover,  deposit  mutton-tallow  when 
this  is  fed  to  them. 

Unlike  the  absorption  of  the  carbohydrates  and  the  pro- 
teins, which  leave  the  alimentary  tract  with  the  blood  stream, 
the  fats  leave  the  absorptive  mucous  membrane  almost  en- 
tirely by  way  of  the  lymph.  Very  shortly  after  a  fatty  meal 
the  lymph  leaving  the  intestine  assumes  a  milky  appearance, 
owing  to  the  exceedingly  fine  droplets  of  fat  contained  in  it, 
and  at  the  height  of  absorption  may  contain  from  3  to  8  per- 
cent of  fat.  The  lymph  returning  from  the  intestine  and 
thus  laden  with  fat  is  known  as  chyle.  Munk  and  Rosen- 
stein found  that  more  than  60  percent  of  the  fat  consumed 
by  their  patient  with  a  lymphatic  fistula  could  be  recovered 
from  the  lymph  within  the  first  twelve  hours  after  feeding. 

1  Rosenfeld:  Verhandlungen  d.  XVII.  Congress  f.  innere  Medicin, 
1899,  p.  503. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.     295 

Some  fat  seems,  however,  to  be  carried  from  the  intestine 
by  way  of  the  blood-vessels,  and  when  the  thoracic  duel  has 
been  ligated  the  amount  carried  in  this  way  is  much  increased. 
Munk  and  Friedenthal  found  that  the  fat  in  the  blood 
may  under  circumstances  rise  to  six  times  the  normal  amount 
when  the  thoracic  duct  is  occluded.  A  thick  layer  of  fat 
forms  upon  the  blood  collected  from  a  vein  even  though 
the  entire  amount  of  fat  absorbed  from  the  intestine  may 
be  less  than  half  that  absorbed  when  the  thoracic  duct  is 
open. 

The  total  amount  of  fat  absorbed  is  dependent  upon  the 
kind  of  fat  fed  an  animal.  We  know  from  Munk  and 
Muller's  observations  that  fats  having  a  low  melting-point 
are  more  perfectly  absorbed  than  those  having  a  higher  one. 
97.7  percent  of  the  olive-oil  fed  an  animal  is  absorbed. 
97.5  percent  of  fats  melting  between  25°  and  34°  C.  (goose- 
and  pork-fat),  90  to  92.5  percent  of  fats  melting  between  49° 
and  51°  C.  (mutton- tallow) ,  and  only  89.4  percent  of  a  mix- 
ture of  stearin  and  almond-oil  melting  at  55°  C.  are  absorbed. 
Of  pure  stearin,  which  does  not  melt  until  60°  C.  is  reached, 
only  9  to  14  percent  is  absorbed.1  When  a  mixture  of  fats 
having  different  melting-points  is  fed,  those  having  the  lower 
melting-points  are  absorbed  more  completely  than  those 
having  the  higher.  Fat  is  also  more  perfectly  absorbed 
when  it  is  free  in  the  form  of  butter  or  lard  than  when  it  is 
enclosed  in  cells,  as  in  fat  meat  or  bacon.  Under  these  cir- 
cumstances the  digestive  juices  must  first  dissolve  the  walls 
of  the  cells. 

The  velocity  with  which  different  fats  are  absorbed  is  also 
determined  in  large  part  by  their  melting-points.  .Mink 
and  Rosenstein  found  that  the  lymph  obtained  from  their 
patient  with  a  lymphatic  fistula  became  milky  in  appear- 
ance two  hours  after  feeding  a  mixture  of  olive-oil  containing 
6  percent  oleic  acid,  and  in  the  fifth  hour  after  feeding  con- 

1  Munk:  Ergebnisse  d.  Physiol.,  1902,  I,  Lie  Al.th.,  p.  323. 


296  PHYSIOLOGY  OF  ALIMENTATION. 

tained  a  maximum  of  4^  percent  fat.  When  mutton-tallow 
was  fed  a  maximum  of  3.8  percent  fat  in  the  lymph  was  not 
reached  until  the  seventh  or  eighth  hour.  The  consump- 
tion of  a  fat  melting  at  53°  C.  did  not  lead  to  more  than  a 
milkiness  of  the  lymph  in  the  fifth  to  the  sixth  hour  (only 
0.7  percent  fat),  which  continued  with  a  progressive  fall  in 
the  percentage  of  "fat  until  the  thirteenth  hour. 

This  is,  perhaps,  the  best  place  at  which  to  discuss  the 
importance  of  the  bile  and  the  pancreas  in  the  absorption 
of  fats.  This  question  is  of  clinical  moment,  for  a  de- 
ficient secretion  or  total  lack  of  bile  or  pancreatic  juice  is 
encountered  in  a  number  of  pathological  conditions.  All 
authors  are  agreed  that  when  experimentally  or  through 
pathological  states  the  bile  is  prevented  from  entering  the 
duodenum  the  fats  are  much  less  perfectly  absorbed  than 
under  normal  circumstances.  This  fact  was  recognized  half  a 
century  ago  by  Bidder  and  Schmidt,  and  has  since  then  been 
corroborated  and  amplified  by  a  score  of  investigators.  The 
exact  amount  of  fat  absorbed  by  men  or  animals  when  no 
bile  enters  the  intestine  is  subject  to  great  variation,  so  that 
it  is  not  surprising  that  the  figures  of  different  students  of 
the  question  vary  greatly.  It  is  ordinarily  stated  that  less 
than  half  of  the  fat  which  under  normal  circumstances 
readily  disappears  from  the  alimentary  tract  is  absorbed 
when  no  bile  is  present.  The  highest  figures  ever  attained 
are  the  disappearance  of  70  percent  of  the  fat  against  95 
percent  in  normal  animals  as  determined  by  analysis  of  the 
faeces.  The  character  of  the  consumed  fat  plays  an  im- 
portant role.  A  fat  with  a  low  melting-point  is  more  readily 
absorbed  than  one  with  a  higher  one,  just  as  under  normal 
circumstances.1  Munk  found  that  the  absorption  of  mutton- 
tallow,  for  example,  was  interfered  with  twice  as  much  as 
the  absorption  of  pork-fat.  A  further  interesting  fact  which 
at  present  still  lacks  an  explanation  is  that  the  proportion 

1  Munk:  Ergebnisse  d.  Physiol.,  1902, 1,  lte  Abth.,  p.  324. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.     297 

of  fatty  acids  to  fat  in  the  faeces  is  much  lusher  when  no  bile 
is  present  than  when  it  is.  Normally,  two-thirds  to  seven- 
tenths  of  the  fatty  substances  present  in  the  fasces  are  fatty 
acids,  while  in  the  absence  of  bile  eight-tenths  to  nine-tenths 
are  fatty  acids,  the  rest  neutral  fat.  It  was  formerly  believed 
that  this  could  be  explained  through  Moore  and  Rock- 
wood's  observation  that  the  fatty  acids  are  more  soluble  in 
the  presence  of  bile  and  hence  are  more  readily  absorbed 
when  this  secretion  is  present,  but  Munk  has  shown  that 
the  reverse  is  true  by  finding  that  fatty  acids  are  more  readily 
absorbed  than  neutral  fats  in  the  absence  of  bile. 

The  many  observations  at  hand  on  the  effect  of  removal 
of  the  pancreas  or  ligation  of  its  duct  all  agree  that  the  absorp- 
tion of  fat  is  much  hampered  by  such  procedures.  Vastly 
different  figures  are,  however,  found  in  the  literature  to 
illustrate  the  extent  to  which  the  absorption  of  fats  is  de- 
creased. When  not  in  the  form  of  an  emulsion  fats  are 
absorbed  in  very  slight  measure  when  the  pancreatic  secretion 
is  entirely  lacking.  Hedon  and  Ville  state  that  10  percent 
of  an  olive-oil  feeding  may  be  absorbed  and  22  percent  of  the 
fat  of  milk.  Minkowski  and  Abelmann  give  even  higher 
figures  for  the  absorption  of  oil  in  the  form  of  an  emulsion, 
28  to  53  percent  of  milk-fat.1  That  any  fat  at  all  should  be 
absorbed  in  the  absence  of  a  pancreatic  secretion  was  long 
regarded  as  a  remarkable  fact.  This  can  no  longer  be  con- 
sidered a  mystery  since  we  have  become  acquainted  with 
the  almost  universal  distribution  of  lipase  in  the  tissues  and 
fluids  of  the  body.  The  mucous  membrane  of  the  small 
intestine  contains  this  ferment,  and  no  doubt  some  is  found 
in  the  secretions  of  this  viscus.  To  the  ferment  present  from 
these  sources  must  be  attributed  whatever  digestion  and 
absorption  of  fat  we  may  encounter  in  an  animal  deprived 
of  its  pancreatic  secretion.  With  the  limited  amount  of 
lipase  present   under    these   circumstances    it   cannot    seem 

1  Quoted  from  Munk,  1.  c,  p.  325. 


298  PHYSIOLOGY  OF  ALIMENTATION. 

strange  that  an  emulsion  of  a  fat  with  its  larger  surface  should 
be  better  absorbed  than  the  same  fat  when  not  previously 
emulsified.  It  is  self-evident  that  with  a  deficient  amount 
of  lipase  the  conditions  normally  provided  for  the  rapid 
production  of  an  emulsion  from  the  fat  of  the  food  are  much 
impaired. 

The  destruction  of  lipase  through  the  gastric  secretions 
has  already  been  pointed  out.  When  fed  in  the  form  of  raw 
chopped  pancreas  some  seems,  however,  to  reach  the  small 
intestine  in  an  uninjured  state.  It  is  a  fact  of  clinical  im- 
portance, therefore,  that  Sandmeyer  has  found  that  the  ab- 
sorption of  fats  in  dogs  deprived  of  their  pancreas  is  much 
increased  through  the  feeding  of  raw  minced  pancreas. 


CHAPTER  XVII. 

THE    ALIMENTARY   TRACT   AS   AN   ABSORPTIVE     SYSTEM. 

{Concluded). 

io.  The  Absorption  of  Proteins. — Since  the  proteins,  un- 
like the  salts  and  water,  and  like  the  fats  and  certain  carbo- 
hydrates, suffer  profound  changes  in  their  passage  through 
the  alimentary  tract,  the  question  arises  first,  of  all,  Are  the 
proteins  absorbed  entirely  or  in  part  as  such,  or  do  they  first 
suffer  a  decomposition  into  simpler  substances  before  they 
pass  through  the  absorbing  wall  of  the  intestinal  tract? 

Physico-chemical  reasons  indicate  that  the  proteins  are  not 
absorbed  as  such,  or  only  in  very  small  amounts,  for  belong- 
ing as  they  do  to  the  general  class  of  the  colloids  they  are  not 
able,  practically  speaking,  to  diffuse  through  a  colloidal  mem- 
brane such  as  the  alimentary  tract  presents.  Experimental 
facts  agree  entirely  with  this  reasoning.  As  Friedlander's  l 
experiments  have  shown,  acid-albumin  does  not  disappear 
when  introduced  into  a  well-washed  loop  of  intestine.  In 
opposition  to  this  are  the  experimental  results  of  most  other 
observers.  Brucke,  Y<>it,  Bauer,  Czerny,  Latschenberger, 
Neumeister,  and  Mink  all  believe  that  no  inconsiderable 
amounts  of  such  substances  as  egg-albumin,  myosin,  blood- 
serum,  and  acid-albumin  can  be  absorbed  as  such  from  care- 
fully cleaned  loops  of  intestine  in  I  he  course  of  one  to  four 
hours.  The  disappearance  of  even  10  or  20  percenl  of  the 
protein  introduced  in  this  way  does  not  prove  necessarily 
thai  it  was  absorbed  in  the  "  native  "  state.    The  fact  that  the 

1  Fkikim.animj;,  Zeitschr.  f.  Biol.,  1896  XXXIII,  ]>.  274. 

299 


300  PHYSIOLOGY  OF  ALIMENTATION. 

amount  of  peptones  in  the  blood  leaving  the  intestines  is  not 
increased  is  an  inconclusive  argument,  for  they  are  not  in- 
creased to  any  marked  degree  even  under  conditions  when 
we  know  that  the  protein  is  being  absorbed  in  the  form  of 
the  soluble  digestion  products.  From  our  knowledge  of  the 
almost  universal  distribution  of  proteolytic  enzymes  through- 
out the  tissues  and  fluids  of  the  animal  body  and  their  great 
activity  in  the  living  organism,  it  does  not  seem  too  hazardous 
to  believe  that  even  that  portion  of  a  protein  solution  which 
is  believed  to  be  absorbed  in  the  ' 'native  "  state  is  in  reality 
absorbed  in  the  form  of  peptones,  or  still  more  probably  in 
the  form  of  the  simple  crystalline  products  of  proteolytic 
activity. 

But  even  if  we  allow  that  proteins  may  be  absorbed  as 
such  the  amount  that  passes  through  the  wall  of  the  alimen- 
tary tract  in  this  form  must  be  small.  Just  how  small  cannot, 
of  course,  be  said,  but  the  knowledge  that  adequate  means 
exist  in  the  body  to  split  all  the  protein  of  an  ordinary  meal 
in  the  course  of  a  few  hours,  and  that  the  diffusion  velocity 
of  even  such  complex  substances  as  the  peptones  is  several 
times  that  of  the  proteins  from  which  they  are  derived,  in- 
dicates that  under  ordinary  circumstances  only  a  small 
fraction,  if  any  at  all,  of  the  protein  of  an  ordinary  meal  is 
absorbed  in  an  unchanged  state. 

If  protein  is  not  absorbed  as  such,  then  in  which  of  the 
various  forms  into  which  it  is  changed  under  the  influence 
of  the  proteolytic  ferments  is  it  absorbed?  This  is  a  ques- 
tion which  it  is  exceedingly  difficult  to  answer,  for  the  multi- 
tude of  experiments  that  have  been  performed  by  many 
different  investigators  have  not  in  any  sense  yielded  results 
which  are  either  entirely  satisfactory  or  capable  of  only  one 
interpretation.  The  burden  of  experimental  evidence  seems 
to  indicate,  however,  that  most,  if  not  all,  protein  is  absorbed 
in  the  form  of  the  very  simple  crystalline  products  of  pro- 
teolysis with  which  we  became  acquainted  in  the  discussion 
of  acid-  and  alkali-pro teinase  (pepsin  and  trypsin),  and  pro- 


alimentary  tract  as  an  absorptive  system.   301 

tease  (erepsin).  The  arguments  which  point  in  this  direction 
are  the  following:  The  proteoses  still  stand  close  to  the  -so- 
called  "typical"  colloids,  and  their  absorption  as  such  is 
open  to  the  same  objections  from  a  physico-chemical  stand- 
point which  were  raised  against  the  albumins  from  which 
they  are  derived.  The  same  holds  true  of  many  of  the 
peptones  (in  Kuhne's  sense),  though  some  of  them  approxi- 
mate the  crystalloids  in  their  physical  behavior.  In  any 
case,  both  classes  of  substances  are  readily  decomposed  under 
the  conditions  existing  in  the  body.  As  agencies  bringing 
about  such  a  decomposition  we  have  the  already-mentioned 
proteolytic  ferments.  Recent  work  indicates  that  acid-pro- 
tcinase  approximates  at  least  qualitatively  the  proteolytic 
activity  of  alkali-proteinase,  and  in  protease  we  have  a  newly 
discovered  ferment  which  seems  to  be  most  energetic  in  break- 
ing down  proteoses  and  peptones  into  the  simple  crystalline 
products  which  have  long  been  considered  characteristic  of 
the  activity  of  alkali-proteinase  (trypsin).  Finally,  if  the 
proteins  are  really  broken  up  into  simple  crystalline  sub- 
stances before  being  absorbed  it  ought  to  be  possible  to  find 
them  in  the  alimentary  contents.  This  has  been  done  by 
Kutscher  and  Seemann,  who  succeeded  in  obtaining  leucin, 
tyrosin,  and  lysin  from  the  intestinal  contents  of  the  dog. 
The  amount  which  they  obtained  was  not  large,  and  this  is 
often  taken  as  an  argument  to  show  that  not  all  or  even  a 
large  part  of  the  protein  of  a  meal  is  split  as  far  as  the  mono- 
and  diamino-acids.  The  objection  is  perhaps  scarcely  a 
valid  one,  for  not  only  are  these  substances  readily  diffusible 
so  that  a  collection  of  a  considerable  amount  is  rendered 
well-nigh  impossible,  but  all  the  proteolytic  change  does  not 
occur  in  the  lumen  of  the  gut;  part  takes  place  in  the  wall 
of  the  intestine,  where  protease  (erepsin)  is  present  in  large 
amounts  and  into  which  :i1  least  some  of  the  peptones  diffuse 
easily.  All  these  facts  seem  to  indicate,  therefore,  thai  the 
proteins  are  absorbed,  nl  leasl  in  the  main,  in  (he  form  of 
the  simplest  digestion  products. 


302  PHYSIOLOGY  OF  ALIMENTATION. 

Through  what  channel  or  channels  are  the  proteins  carried 
away  from  the  alimentary  tract?  It  has  been  found  that 
the  same  holds  true  here  as  in  the  case  of  the  carbohydrates. 
Under  ordinary  circumstances  practically  all  the  protein  of 
a  meal  passes  from  the  alimentary  tract  through  the  blood- 
vessels and  only  when  excessive  amounts  are  fed  does  a  small 
percent  pass  over  into  the  lymphatic  circulation.  Schmidt- 
Mulheim  showed  this  to  be  true  when  he  found  that  the  ab- 
sorption of  the  proteins  from  the  alimentary  tract  is  not 
impeded  when  the  main  lymphatic  channels  coming  from 
the  alimentary  tract  are  tied  off.  Munk  and  Rosenstein's  l 
studies  on  a  patient  with  a  lymphatic  fistula  through  which 
most  of  the  visceral  lymph  was  poured  out  externally  show 
this  in  a  still  better  way.  When  80  to  103  grams  of  lean  meat 
were  fed  this  patient  at  a  single  meal  (which  more  than 
covers  the  entire  amount  of  protein  consumed  by  the  ordi- 
nary individual  in  a  day)  it  was  found  that  neither  the  total 
amount  of  lymph  nor  the  percent  of  nitrogen  in  the  lymph 
was  markedly  increased  during  the  twelve  hours  following 
the  meal.  L.  B.  Mendel  2  has  come  to  similar  conclusions 
from  his  experiments  on  dogs.  Even  when  excessive  amounts 
of  protein  are  fed  scarcely  more  than  one-fifteenth  of  the 
whole  amount  that  is  absorbed  passes  from  the  alimentary 
tract  through  the  lymphatics. 

The  relative  importance  of  the  stomach  and  of  the  intestine 
with  its  attached  pancreas  as  organs  concerned  in  the  diges- 
tion and  absorption  of  the  proteins  is  somewhat  difficult  to 
determine,  and  the  data  we  have  at  our  disposal  vary  greatly. 
Since  Czerny,  in  1878,  removed  the  entire  stomach  of  a  dog 
and  kept  him  in  good  health  for  six  years  afterward  (when  he 
was  killed  for  study)  no  one  has  seriously  questioned  the 
statement  that  the  stomach  is  not  essential  to  good  health, 
provided  only  a  proper  diet  be  observed.    Ludwig  and  Ogata 

'Munk  and  Rosenstein:  Ergebnisse  d.  Physiologie,  1902, 1,  lte 
Abth...  p.  312. 

2  L.  B.  Mendel:  American  Jour,  of  Physiol.,  1899,  II,  p.  137. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.     303 

were  able  to  show  that  the  nitrogenous  excretion  of  dogs 
could  be  covered  entirely  through  the  nitrogen  obtained 
from  finely  minced  meat,  eggs,  h<\.  introduced  directly  into 
the  duodenum  through  a  fistula,  and  more  recently  a  number 
of  operations  carried  out  on  human  beings  in  which  all  or 
nearly  all  the  stomach  lias  been  removed  have  shown  that 
absence  of  this  organ  does  not  jeopardize  life.  •  The  pan- 
creas with  the  small  intestine  is  able  to  take  care  of  all  the 
protein  necessary  for  the  life  of  the  individual.  For  reasons 
which  have  already  been  pointed  out,  such  patients  do  best 
on  sterile  food,  for  the  gastric  juice  is  no  longer  present  to 
reduce  the  number  of  bacteria  consumed  with  the  ordinary 
food;  and  since  an  organ  is  no  longer  present  which  acts  as  a 
reservoir  for  the  food  and  gives  small  amounts  periodically 
to  the  intestine,  repeated  feedings  only  can  be  well  tolerated. 
Since  the  acid  of  the  gastric  juice  is  best  able  of  all  the  ali- 
mentary secretions  to  act  upon  the  connective  tissues,  these 
appear  in  the  fseces  after  the  stomach  is  gone. 

The  experiments  which  have  been  made  to  determine  the 
importance  of  the  stomach  as  an  absorptive  organ  for  the 
proteins  are  not  free  from  criticism.  They  seem  to  indicate, 
however,  that  a  small  percent,  perhaps,  of  the  total  amount 
of  the  protein  in  an  ordinary  meal  may  be  absorbed  by  the 
gastric  mucous  membrane.  As  the  chief  absorptive  organ 
of  the  proteins  we  must  regard  the  small  intestine,  more 
especially  the  upper  half.  This  absorptive  power  decreases 
apparently  from  above  downwards,  reaching  a  very  low 
grade  in  the  large  intestine. 

According  to  most  observers  the  pancreas  plays  a  much 
heavier  role  than  the  stomach  in  the  digestion  of  the 
proteins.  To  till  extirpation  of  the  pancreas  is  fatal,  for  this 
is  followed  by  a  diabetes  which  ends  the  life  of  its  vic- 
tim in  a  few  days.  For  this  reason  it,  becomes  necessary  in 
experiments  on  the  digestive  functions  of  the  pancreas  to 
limit  oneself  to  occlusion  of  the  pancreatic  duct  or  duct--  by 
means  of  ligatures,  or  to  only  partial  excision  of  the  pancr 


304  PHYSIOLOGY  OF  ALIMENTATION. 

or  total  excision  with  transplantation  of  a  portion  of  the 
organ  to  some  other  part  of  the  body.  These  various  pro- 
cedures have  been  adopted  by  different  investigators.  The 
results  obtained  vary  greatly.  All  seem  to  agree,  however, 
fhat  the  digestion  and  absorption  of  proteins  are  interfered 
with  markedly  when  the  pancreatic  juice  no  longer  pours 
into  the  duodenum.  This  is  not  surprising  when  it  is  remem- 
bered how  well  protein  digestion  may  go  on  after  removal 
of  the  stomach.  Generally  speaking,  less  than  half  the  pro- 
tein of  an  ordinary  meal  is  digested  when  the  pancreas  is 
gone.  Harley  found  only  18  percent  digested  after  removal 
of  the  pancreas,  though  Deucher  found  80  percent  utilized 
after  complete  occlusion  of  the  pancreatic  duct.1  The  pro- 
teolytic activity  must  evidently  be  sought  in  these  cases  in 
the  secretion  of  the  stomach,  augmented  by  those  found  in 
the  secretions  and  mucous  membrane  of  the  small  intestine. 

What,  now,  is  the  fate  of  the  protein  which  disappears 
from  the  lumen  of  the  alimentary  tract?  Of  fundamental 
importance  is  the  fact  that  even  after  a  meal  rich  in  proteins 
neither  peptones  nor  proteoses  appear  in  either  the  blood  or 
the  lymph.  This  has  been  shown  to  be  true  in  various  ways : 
Direct  analysis  of  the  blood  leaving  the  intestine  points  in 
this  direction.  Furthermore,  peptones  injected  directly  into 
the  blood  are  excreted  through  the  kidneys,  and  normally 
no  peptones  can  be  found  in  the  urine,  even  after  a  very 
heavy  protein  meal.  The  peptones  lower  the  blood  pressure 
when  injected  into  the  general  circulation,  yet  a  lowered 
blood  pressure  is  never  observed  after  the  consumption  of 
large  amounts  of  protein,  or  even  after  the  introduction  of 
large  amounts  of  peptone  into  the  alimentary  tract.  All  this 
indicates  clearly  that  peptones  do  not  get  into  the  blood  or 
lymph  (at  least  in  sufficient  amounts  to  be  recognized  by 
the  analytical  means  ordinarily  employed).  Nor  do  peptones 
and  proteoses  in  the  blood  issuing  immediately  from  the  in- 

'SeeMraK:    I.e.,  p.  316. 


ALIMENTARY  TRACT  AS  AN  ABSORPTIVE  SYSTEM.      305 

testinc  appear  to  be  caught  and  held  by  some  organ,  such  as 
the  liver  or  spleen,  before  passing  over  into  the  general  cir- 
culation. This  has  been  shown  by  comparative  analyses  of 
the  blood  obtained  from  the  portal  vein,  for  example,  and 
(hat  obtained  from  a  large  artery,  as  well  as  by  the  experi- 
ments already  cited. 

What,  then,  does  become  of  the  proteins  which  enter  the 
alimentary  tract?  It  is  clear  that  if  they  disappear  from  the 
lumen  of  the  intestine  and  cannot  be  discovered  in  the  blood 
leaving  the  alimentary  tract  as  proteoses  and  peptones  they 
must  exist  here  in  some  other  form.  In  what  form  cannot 
be  easily  said,  though  there  are  two  possibilities,  either  or 
both  of  which  may  be  correct,  and  both  of  which  have  ex- 
perimental foundation. 

The  first  of  these  is  that  the  proteins,  be  these  absorbed  in 
whatever  way  we  may  consider  the  correct  one,  are  recon- 
structed in  their  passage  through  the  epithelium  of  the 
stomach  or  intestine  into  complex  albumins  and  globu- 
lins which  we  are  unable  to  distinguish  from  those  found 
normally  in  the  blood.  This  means  that  if  we  believe  all 
the  protein  of  a  meal  to  be  absorbed  in  the  form  of  Kuhne's 
peptones,  or  perhaps  in  the  form  of  mono-  and  diamino- 
acids,  that  these  are  reconverted  into  complex  albumins  in 
passing  through  the  alimentary  wall. 

The  experiments  of  Abderhalden  and  Samuely  l  are  of 
great  interest  in  this  connection.  These  show  that  the  com- 
position of  the  blood,  so  far  as  its  protein  constituents  are 
concerned,  is  apparently  entirely  independent  of  the  char- 
acter of  the  proteins  consumed  by  the  individual.  Analysis 
of  six  litres  of  blood  removed  from  the  veins  of  a  horse  showed 
that  it  contained  protein  bodies  which  yielded  after  hydrol- 
ysis: 

Tyrosin 2 .  43  percent 

Glutamic  acid  8.85      " 

1  Audekhaldkn  and  SaM^ELY:  Zdtsvhr.  1".  physiol,  (.'hem.,  10"), 
XL  VI,  p.  193. 


306  PHYSIOLOGY  OF  ALIMENTATION. 

After  starvation  for  a  week,  in  order  to  free  the  alimentary 
tract  from  food,  analysis  of  another  six  litres  of  blood  yielded 
practically  the  same  results : 

Tyrosin 2 .  60  percent 

Glutamic  acid 8.20      " 

The  horse  was  now  fed  a  protein  (gliadin)  which  is  much 
richer  in  glutamic  acid  than  blood  serum  and  contains  about 
the  same  percent  of  tyrosin.  Even  when  1500  to  2500  grams 
of  the  protein  were  fed  analysis  of  the  blood  showed  prac- 
tically no  variation  in  its  composition.  The  following  table 
gives  the  results  of  three  experiments: 

1500  gms.     1500  gms.     2500  gms. 
Percent.        Percent.         Percent. 

Tyrosin ...2.24         2.52         2.48 

Glutamic  acid 7.88        8.25         8.00 

It  seems,  therefore,  as  though  an  actual  synthesis  of  pro- 
tein occurs  in  the  wall  of  the  intestine  itself.  From  the 
most  varied  kinds  of  protein  consumed  by  an  animal  are  con- 
structed first  of  all  the  serum  albumin  and  serum  globulin  found 
in  the  blood-serum  of  that  animal,  and  from  this  serum,  so 
constant  in  its  composition,  the  different  cells  of  the  body  each 
take  the  substances  necessary  for  their  purposes.  Indirectly 
we  find  in  these  considerations  support  for  the  idea  that  the 
proteins  are  absorbed  from  the  alimentary  tract  only  in  the 
form  of  the  simple  digestion  products,  for  these  can  most 
readily  be  joined  chemically  to  produce  the  protein  bodies 
characteristic  of  the  animal  under  consideration. 

As  Abderhalden  x  has  well  pointed  out,  these  conceptions 
place  the  functions  of  the  alimentary  tract  and  its  enzymes  in 
an  entirely  new  light.  They  together  guarantee  a  proper  met- 
abolism of  the  body  as  a  whole.  The  ferments  through  their 
action  on  the  various  foodstuffs  break  these  up  into  their 
elements,  which  are  the  same  even  when   derived  from  the 

1  Abderhalden:  Lehrbuch  d.  physiol.  Chem.,  Berlin,  1906,  p.  232. 


ALIMENTARY  TRACT  AS  AN  ABSORPTH  E  SYSTEM.     307 

most  varied  parent  bodies.  The  alimentary  trail  then 
synthesizes  from  these  elements  the  complex  substances 
found  in  the  blood.  In  disturbances  in  general  metabolism 
involving  the  alimentary  tract  it  is  not  so  much  the  impaired 
absorption  that  is  so  important  as  the  impaired  assimila- 
tion. That  this  synthesis  of  protein  plays  an  important  role 
in  the  metabolism  of  the  animal  has  been  shown  very  strik- 
ingly by  Abderhalden  and  Roxa.1  These  authors  were  able 
to  keep  animals  in  nitrogenous  equilibrium  by  feeding  them, 
in  addition  to  an  ordinary  mixture  of  fats  and  carbohydrates, 
casein  which  had  been  previously  digested  through  alkali- 
proteinase,  so  that  80  to  85  percent  of  it  consisted  of  amino- 
acids  mixed  with  simple  polypeptides,  the  remaining  15  to  20 
percent  of  more  complex  polypeptides,  but  not  sufficiently 
so  to  give  a  biuret  reaction. 

As  agencies  capable  of  such  a  reconstruction  of  the  albu- 
min molecule  have  been  mentioned  the  chemical  forces  of 
the  epithelial  cells  themselves  and  the  activities  of  Julia 
Biuxck's  micrococcus  restituens.  That  a  microorganism  living 
upon  the  surface  of  the  alimentary  mucous  membrane  should 
be  of  any  importance  to  its  host  by  being  able  to  reconstruct 
from  the  products  of  proteolysis  the  protein  itself  (which 
would  again  have  to  be  broken  up  before  it  could  pass  through 
the  epithelial  cells  in  any  amount)  is,  no  doubt,  too  improb- 
able to  need  serious  consideration.  There  is  much  more  likeli- 
hood that  the  chemical  forces  residing  in  the  epithelial  cells 
are  capable  of  reconstructing  albumins  from  the  products 
of  proteolysis.  Elsewhere2  experiments  have  been  dis- 
cussed which  seem  to  indicate  that  the  activity  of  the  pro- 
teolytic ferments  is  reversible.  Were  this  true,  then  the 
synthesis  of  albumins  within  the  epithelial  cells  lining  the 
alimentary  tract,  in  a  way  entirely  analogous  to  the  syn- 
thesis of  fat    in   this   locality   under   the   influence  of  lipase, 

1  Abdi  rhai  m«  and  Rona:  Zeitschr.  f.  physiol.  Chem.,  1004,  XL1I, 
p.  528;  ibid.,  1005,  XLIV,  p.  10S. 

2  See  p.  140. 


308  PHYSIOLOGY  OF  ALIMENTATION. 

might  readily  be  explained.  The  presence  of  such  ferments 
as  alkali-proteinase  (trypsin)  has  been  demonstrated  not 
only  in  these  cells  but  in  practically  every  cell  and  fluid  of 
the  body. 

A  second  reason  why  the  products  of  proteolysis — prote- 
oses, peptones,  or  amino-acids — do  not  appear  in  the  blood 
leaving  the  intestine  may  reside  in  the  fact  that  they  are  in 
their  passage  through  the  intestinal  wall  broken  into  yet 
simpler  substances.  The  proteinase  and  protease  present 
in  the  cells  of  the  mucosa  may  well  continue  their  work  until 
none  of  the  higher  polypeptides  are  left.  But,  even  if  all  the 
protein  is  first  split  into  the  simple  mono-  and  diamino-acids 
before  passing  into  the  blood,  as  seems  to  be  the  case,  all  these 
acids  need  not  necessarily  go  to  build  up  albumins  and  glob- 
ulins once  more.  They  may  be  broken  into  yet  simpler 
substances.  There  exist  in  the  mucous  membrane  of  the 
alimentary  tract  and  in  various  organs  in  the  body  ferments 
which  are  capable  of  bringing  about  such  a  destruction  of 
mono-  and  diamino-acids.  With  one  such  ferment  we  are 
acquainted,  through  Kossel  and  Dakin's  work  on  arginase, 
which  is  a  ferment  capable  of  acting  upon  arginin  and  split- 
ting this  into  urea  and  ornithin.  The  discovery  of  this  fer- 
ment, as  also  the  well-known  fact  that  the  excretion  of  urea 
in  the  urine  reaches  its  maximum  shortly  after  the  consump- 
tion of  a  protein  meal,  seems  to  indicate  that  a  portion,  at 
least,  of  the  albuminous  bodies  which  constitute  our  food  are 
rapidly  broken  up  into  the  ultimate  products  of  protein  met- 
abolism. Apparently,  therefore,  a  part  of  the  protein  we  ab- 
sorb goes  to  maintain  the  proportion  of  albumin  and  globulin 
found  in  the  blood,  and  so  is  distributed  to  the  cells  and  tissues 
of  the  body,  while  another  serves  as  a  source  of  energy  and 
leaves  the  body  in  the  form  of  urea. 

This  is  perhaps  the  best  place  in  which  to  discuss  the 
physiological  importance  of  protease  (erepsin)  as  a  digestive 
enzyme,  and  of  importance,  in  consequence,  in  the  absorption 
of  the  proteins,     It  is  evident  that  from  the  nature  of  its  action 


ALIMENTARY  TRACT  AS  AN  M'.SORPTIVE  SYSTEM.     309 

alone  it  might  well  play  a  rule  not  inferior  to  thai  of  acid-or 
alkali-proteinase  (pepsin  or  trypsin).  Not  only  does  protease 
act  on  casein  directly,  but  it  is  able  to  bring  about  the  split- 
ting of  proteoses  and  peptones  as  energetically  and  as  rapidly 
as  either  acid-  or  alkali-proteinase.  In  fact,  it  need  not 
surprise  us  if  in  the  near  future  we  discover  that  some  of  the 
cleavages  of  protein  which  we  have  thus  far  attributed  to 
alkali-proteinase  are  in  reality  brought  about  through  the 
protease  existing  beside  the  proteinase  as  an  impurity. 

Protease  is  found  not  only  in  the  secretions  of  the  small 
intestine  but  also  in  the  cells  of  the  intestinal  mucosa.  Since 
much  more  is  found  in  the  latter  location  than  in  the  former, 
it  may  well  be  concluded  that  the  protease  within  the  cells 
is  of  greater  physiological  importance  than  that  contained 
in  the  secretions.  Self-apparent  also  is  the  fact  that  the 
power  of  diffusion  possessed  by  the  proteoses  in  part,  by  the 
peptones  (in  Kuhne's  sense)  in  much  larger  part,  plays  an 
important  role  in  rendering  the  protease  found  in  the  cells 
an  active  agent  in  the  demolition  of  the  protein  molecule. 

The  following  experiment 1  illustrates  the  rapidity  with 
which  a  peptone  solution  disappears  from  the  intestine. 
A  loop  of  intestine  50  cm.  long  is  carefully  taken  out  of  the 
abdominal  cavity  of  a  dog  and  after  being  ligatured  at  both 
ends  is  opened  and  well  washed.  39  c.c.  of  a  peptone  solution 
containing  0.49  gm.  nitrogen  are  introduced  into  the  intestine 
and  the  loop  replaced  in  the  abdominal  cavity.  At  the  end 
of  an  hour  the  loop  is  again  taken  out  and  the  amount  of 
unabsorbed  peptone  solution  determined.  It  is  found  that 
0.29G  gm.  nitrogen  has  been  absorbed,  in  other  words,  over 
60  percent. 

When  the  95  cm.  of  intestine  which  were  not  used  in  this 
experiment  are  taken  into  consideration,  simple  calculation 
shows  that  this  dog  would  have  boon  able  to  absorb  from  its 
entire  small  intestine  more  than  0.8  gm.  nitrogen  per  hour. 

'Coii.nheim:  Zcitsclir.  f.  physiol.  Chemie,  L902,  XXXVI,  p.  13, 


310  PHYSIOLOGY  OF  ALIMENTATION. 

This  figure,  which  is  by  no  means  the  highest  that  might  be 
given  for  experiments  of  this  sort,  indicates  how  rapidly 
peptones  disappear  from  the  small  intestine,  especially  when 
it  is  added  that  at  this  rate  a  dog  could  absorb  in  one  hour 
nearly  enough  nitrogenous  material  to  suffice  for  its  daily 
existence. 

It  remains  for  us  to  show  that  this  rapid  absorption  of 
peptones  is  determined  by  the  action  of  protease  upon  them, 
whereby  they  are  dissociated  into  the  very  diffusible  crystal- 
line digestion-products  which  have  been  enumerated  above; 
and  that  this  dissociation  is  not  brought  about  by  such  a 
ferment  as  alkali-pro teinase  (trypsin).  While  under  ordi- 
nary circumstances  both  alkali-  and  acicl-proteinase  are 
active  in  bringing  about  the  dissociation  of  the  protein  which 
we  take  in  with  our  food,  under  the  experimental  condi- 
tions outlined  above  this  is  not  the  case,  for  a  well-washed 
loop  of  intestine  contains  no  alkali-pro  teinase  (trypsin),  or 
at  best  only  very  little.  This  has  been  repeatedly  shown 
by  experiments  in  which  proteins,  such  as  fibrin,  are  intro- 
duced directly  into  the  small  intestine,  when  it  has  been 
found  that  they  disappear  very  slowly  (in  days  or  even 
weeks). 


CHAPTER  XVIII. 
THE   ALIMENTARY   TRACT   AS   AN   EXCRETORY   SYSTEM. 

i.  General   Clinical  and  Experimental  Considerations. — 

Practical  medicine  has  for  a  long  time  recognized  empirically 
the  function  of  the  alimentary  tract  as  an  organ  of  excretion. 
As  an  example  we  need  only  cite  the  practice  of  purgation 
in  cases  of  renal  disease,  in  which  the  effort  is  made  to  carry 
off  the  poisonous  metabolic  products  of  the  body  through 
the  intestinal  tract.  The  beneficial  effects  following  this 
therapeutic  procedure  are  illustrated  in  the  clinical  experi- 
ences of  every  day. 

The  scientific  basis  of  this  practice  has  not  as  yet  been 
definitely  established  through  experiment.  It  is  true  that 
there  exist  a  large  number  of  isolated  facts,  which  show  that 
various  poisons,  no  matter  how  introduced  into  the  living 
organism,  are  eliminated  through  the  alimentary  tract.  Every 
physician  is  acquainted  with  the  elimination  of  the  iodides 
through  the  salivary  glands  after  introduction  of  these  salts 
into  the  stomach; l  with  the  elimination  of  arsenic  and  mor- 
phin2  through  the  stomach,  even  when  these  substances 
do  not  enter  the  organism  through  the  intestinal  tract, 
and  with  the  excretion  of  iron  compounds  through  the  small 
intestine.     Mendel  and  Thacher3  have  recently  collected  a 

1  Penzoldt  and  Faber:  Berliner  klin.  Wochenschr.,  1SS2,  XIX, 
p.  363. 

2  Kunkel:  Handbuch  d.  Toxicologic,  1901,  p.  54. 

3  Mendel  and  Thacher:  American  Journal  of  Physiology,  1904, 
XI,  p.  5. 

311 


312  PHYSIOLOGY  OF   ALIMENTATION. 

large  number  of  instances  illustrating  the  fact  that  various 
organic  and  inorganic  substances  are  eliminated  through  the 
alimentary  tract.  For  the  most  part,  however,  quantitative 
determinations,  showing  the  amounts  of  the  various  sub- 
stances eliminated  in  this  way  and  the  amounts  cast  off 
through  the  other  emunctories  of  the  body,  for  instance,  the 
kidneys  and  skin,  have  not  been  made  in  these  earlier  experi- 
mental studies. 

With  the  especial  purpose  of  determining  the  relative  im- 
portance of  the  kidneys  and  alimentary  tract  as  organs  of 
excretion  for  certain  of  the  inorganic  compounds,  Mendel  and 
his  pupils,  Hanford  and  Thacher,  have  taken  up  this 
problem.1 

Mendel  and  Thacher  used  strontium  (in  the  form  of  stron- 
tium acetate)  in  their  experimental  studies,  as  this  is  an  ele- 
ment which  does  not  occur  normally  in  the  ordinary  labora- 
tory animals,  and  hence  can  be  readily  recognized  in  the 
different  tissues  spectroscopically.  As  the  experiments  were 
designed  to  determine  the  function  of  the  alimentary  tract 
as  an  excretory  organ  the  salt  could  not  be  given  by  mouth. 
A  four  percent  solution  of  strontium  acetate  was  in  conse- 
quence injected  subcutaneously  with  all  aseptic  precautions,  or 
at  times  intraperitoneally  or  intravenously.  The  animals  were 
kept  in  metallic  cages  and  the  urine  and  faeces  collected 
separately.  A  series  of  experiments  performed  on  dogs,  cats, 
and  rabbits  yielded  the  following  interesting  results. 

Strontium  is  eliminated  only  to  a  small  extent  through  the 
kidneys,  even  when  this  element  is  introduced  in  the  form  of 
a  salt  directly  into  the  circulation.  The  excretion  in  the 
urine  begins  shortly  after  the  injection  and  usually  ceases 
within  twenty-four  hours.  By  far  the  larger  portion  of  the 
strontium  is  excreted  through  the  fseces,  and  it  is  immaterial 
how  the  element  has  been  given.     The  place  of  excretion  is 


1  Hanford:  American    Journal    of  Physiology,   1903,  IX,    p.  235; 
Mendel  and  Thacher:  ibid.,  1904,  XI,  p.  7, 


ALIMENTARY  TRACT  AS  AN  EXCRETORY  SYSTEM.      313 

apparently  limited  to  the  region  of  the  alimentary  tract  be- 
yond the  stomach. 

The  following  experiments  will  serve  to  illustrate  the  fore- 
going. As  strontium  tends  to  be  stored  in  certain  tissues  of 
the  body  and  is  only  eliminated  slowly,  the  dejecta  of  the 
animals  experimented  upon  have  to  be  studied  for  several 
days.  A  dog  weighing  6  kilos  received  a  number  of  subcu- 
taneous strontium  acetate  injections,  the  total  amount  of 
strontium  injected  being  0.543  gm.  The  urine  and  faeces 
were  collected  separately  for  21  days.  The  total  urine  con- 
tained an  unweighable  trace  of  strontium.  The  total  fseces 
contained  0.0998  gm.  of  this  element. 

At  times,  however,  a  much  larger  percentage  of  the  injected 
strontium  can  be  recovered.  A  dog  weighing  14  kilos  was 
given  0.28  gm.  strontium  (in  the  form  of  the  acetate)  sub- 
cutaneously.  At  no  time  for  17  days  subsequently  could 
strontium  be  detected  in  the  urine.  From  the  faeces  0.237 
gm.  were  recovered  during  this  period.1 

In  a  series  of  experiments  which  Professor  Mendel  2  has 
communicated  to  me  by  letter,  he  has  been  able  to  show  that 
barium  behaves  not  unlike  strontium.  If  barium  chloride  is 
introduced  into  the  body  even  in  other  ways  than  through 
the  mouth,  it  is  eliminated  almost  exclusively  by  the  intes- 
tinal tract.  After  the  first  twenty-four  or  forty-eight  hours 
the  urine  shows  no  signs  of  containing  the  element  barium, 
even  though  the  faeces  contain  the  substance  for  days  after- 
ward. Barium  tends  to  be  stored  in  the  body  even  more 
readily  than  strontium  and  so  is  eliminated  more  slowly. 

Rubidium  belongs  in  the  class  with  sodium,  and  like  this 
leaves  the  body  chiefly  through  the  kidneys.  To  a  certain 
extent,  however,  rubidium  also  is  eliminated  through  the 
intestinal  tract. 


1  Mendel  and  Thachek:  American  Journal  of  Physiology    L904,  XI 
p   14. 

2  Personal  letter  dated  New  Baven,  Connectieut,  July  123,  1905. 


314  PHYSIOLOGY  OF  ALIMENTATION. 

The  question  of  the  excretory  function  of  the  alimentary- 
tract  has  also  been  studied  by  J.  B.  MacCallum.1  This  ob- 
server has  confirmed  the  experiments  of  some  of  the  older 
students  of  oedema  that  sodium-chloride  solutions  of  the 
osmotic  concentration  of  the  blood,  or  somewhat  higher,  - 
when  injected  into  the  circulation  of  rabbits,  cause  a  greatly 
increased  secretion  of  fluid  into  the  intestinal  tract.  The 
amount  of  fluid  eliminated  in  this  way  varies  both  with  the 
rate  and  the  quantity  of  the  salt  solution  that  is  injected. 
In  one  experiment  in  which  500  c.c.  of  salt  solution  were 
injected  intravenously,  14.46  percent  were  eliminated  through 
the  intestinal  tract.  In  another  experiment  9  percent  of 
the  total  quantity  of  fluid  injected  was  eliminated  in  this 
way,  and  in  a  third,  10.25  percent.  When  the  kidneys  are 
removed  the  amount  excreted  through  the  intestine  is  some- 
what higher — 16.6  percent  in  one  experiment.  The  intes- 
tinal tract  behaves  therefore  not  unlike  the  kidneys  under 
similar  circumstances.  We  are  well  acquainted  with  the 
effect  of  intravenous  injections  of  salt  solutions  in  increasing 
the  output  of  urine.  The  increased  secretion  from  the  intes- 
tinal tract  is  therefore  not  unlike  the  polyuria  brought 
about  by  similar  means. 

Interestingly  enough,  the  other  salts  which  bring  about 
an  increased  secretion  of  urine  also  bring  about  in  a  similar 
way  an  increased  secretion  from  the  intestine.  Experiment 
has  shown  that  the  diuretic  salts  and  the  saline  cathartics 
are  the  same.  So  far  as  the  excretion  of  water  from  the  body 
is  concerned,  therefore,  we  may  well  look  upon  the  intestinal 
tract  as  supplementary  to  the  kidneys. 

MacCallum  made  no  determinations  of  the  relative  amounts 
of  the  various  salts  which  are  eliminated  through  the  kidneys 
and  intestine.  It  is  clear  from  Mendel's  experiments,  how- 
ever, that  these  must  differ  with  the  different  elements.     The 


1  MacCallum:   University  of    California  Publications,   Physiology, 
1904, 1,  p.  125. 


ALIMENT  l/.T  TRACT  AS  AN  EXCRETORY  SYSTEM.    315 

former  has,  however,  found  in  his  own  experiments  and  had 
collected  facts  from  the  litera  fcure  which  sh  >w  tha  I  lubstances 
which  are  ordinarily  believed  to  be  excreted  chiefly  or  ex- 
clusively through  the  kidneys  are  eliminated  also  by  the 
intestine.  Claude  Bernard  found  as  far  back  as  L859  that 
urea  occurs  in  the  saliva  and  the  gastric  juice,  and  tli.it  in 
nephritis  and  after  removal  of  the  kidneys  this  substance  is 
excreted  to  a  large  extent  by  the  intestine.  From  this  fact 
Claude  Bernard  concludes  that  the  intestine  may  supple- 
ment the  kidneys  in  eliminating  the  various  constituents  of 
the  urine.  The  presence  of  urea  in  the  intestinal  juice  of 
sheep  has  been  demonstrated  by  Pregl,  and  MacCallum 
found  this  substance  normally  present  in  the  same  secretion 
of  the  rabbit. 

Of  great  interest  is  the  fact  discovered  by  MacCallum  that 
in  a  certain  form  of  experimental  diabetes  the  sugar  is  elimi- 
nated, not  only  by  the  kidneys  but  also  through  the  intestinal 
tract.  As  first  shown  by  Bock  and  Hoffmann  and  con- 
firmed by  KtJLz's  and  my  own  experiments,  the  intravenous 
injection  of  rabbits  with  a  sodium  chloride  solution  of  a  some- 
what higher  concentration  than  the  sodium  chloride  in  the 
blood  brings  about  a  transient  excretion  of  glucose  in  the 
urine.1  The  observations  of  MacCallum  show  that  under 
these  conditions  sugar  is  eliminated  also  by  the  stomach  and 
intestine  and  apparently  in  about  the  same  concentration  as 
in  the  urine.  The  excretion  of  the  carbohydrate  through 
the  intestinal  trad  can  he  made  more  apparent  by  removing 
the  kidneys,  but  even  when  they  are  left  intact,  sugar  is 
nevertheless  excreted  to  some  extent  through  the  alimentary 
tract.  How  great  a  role  this  route  of  excretion  plays  in  the 
ordinary  cases  of  human  diabetes  is  an  interesting  question 
which  has  not  as  yet  been  investigated.2 

'Martin  II.  Fischer:  University  of  California  Publications,  Physi- 
ology, 1903,  I .  pp.  77  : x 1 1 <  1  s7;  l'i  i  Bgj  r's  AjTchiv.,  1904, CVJ .  p.  80;  ibid., 
1905,  CI X,  p.  1. 

2  My  analysis  of  the  fircos  in  two  cat      of    human  diabetes    failed 


316  PHYSIOLOGY  OF  ALIMENTATION. 

The  above  facts,  to  which  many  more  could  be  added 
from  medical  literature,  begin  to  give  us  an  experimental 
foundation  for  the  long-established  empirical  practice  of 
utilizing  the  intestinal  tract  as  an  organ  of  excretion  in  those 
diseases  in  which  the  function  of  the  kidneys  is  impaired. 
Not  only  has  it  been  shown  that  for  many  substances  the  in- 
testinal tract  is  the  chief  excretory  organ,  but  also  that  the 
intestine  behaves  in  many  respects  not  unlike  the  kidneys. 
The  same  salts  which  act  as  diuretics  act  as  cathartics,  and 
sugar  and  urea,  which  by  many  have  been  looked  upon  as 
substances  excreted  only  by  the  kidneys,  may  be  lost  from 
the  body  through  the  intestinal  tract  also. 

The  problems  which  suggest  themselves  in  this  domain  of 
the  excretory  function  of  the  alimentary  tract,  so  often  touched 
upon  but  so  little  studied,  are  many.  In  how  far  can  we  sub- 
stitute the  activity  of  the  intestinal  tract  as  an  excretory 
organ  for  that  of  the  kidneys  in  ridding  the  organism  of  the 
various  substances  found  in  the  urine  both  in  health  and 
disease?  Each  of  the  substances  found  in  this  excretion, 
from  the  ordinary  salts  to  the  most  complex  organic  poisons, 
such  as  the  toxins,  will  have  to  be  investigated  with  this 
problem  in  mind,  and  the  results  obtained  may  well  be  ex- 


to  show  sugar  in  sufficient  amounts  to  be  recognized  by  ordinary 
laboratory  methods  even  when  600  to  700  grams  of  sugar  were  being 
excreted  in  the  urine.  According  to  experiments  carried  on  with 
Gertrude  Moore,  practically  no  sugar  escapes  through  the  gastro- 
intestinal tract  in  rabbits  rendered  diabetic  through  puncture  of  the 
medulla.  But  this  happens  in  such  rabbits  as  soon  as  a  sodium 
chloride  solution  is  injected  intravenously.  A  sodium  chloride  solu- 
tion too  dilute  to  bring  about  a  glycosuria  by  itself  is  able  to  do  this. 
The  sodium  chloride  therefore  renders  the  gastro-intestinal  mucosa 
permeable  in  one  direction  to  a  substance  to  which  it  was  formerly 
impermeable.  An  analysis  of  MacCallum's  experiments  shows  that 
he  never  injected  sodium  chloride  in  sufficient  amounts  to  bring  about 
a  glycosuria.  He  rendered  his  rabbits  diabetic  through  the  use  of 
morphin,  and  obtained  sugar  in  the  gastro-intestinal  secretions  through 
subsequent  intravenous  injections  of  sodium  chloride  solutions. 


ALIMENTARY  TRACT  AS  AN  EXCRETORY  SYSTEM.      317 

peeted  to  be  of  the  utmost  practical  value  in  medicine.  It 
was  shown  above  to  how  great  an  extent  certain  inorganic- 
substances  are  eliminated  by  the  alimentary  tract.  Flexner 
has  found  that  the  toxin  of  the  Shiga  bacillus,  no  matter 
how  introduced  into  the  body,  is  eliminated  through  the 
intestinal  tract,  and  in  this  elimination  gives  rise  to  the 
ulcers  found  in  the  dysentery  produced  by  this  organism. 
The  recognition  of  the  fact  that  morphin  is  secreted  into 
the  stomach,  even  when  subcutaneously  introduced,  has  led 
to  the  practice  of  gastric  lavage  for  morphin  poisoning;  and  the 
knowledge  that  arsenic  appears  in  the  gastro-intestinal  tract, 
no  matter  how  it  is  given,  has  led  to  scientific  methods  of 
recognizing  cases  of  poisoning  by  this  element,  not  only  for 
diagnostic  but  also  for  medico-legal  purposes. 

2.  The  Character  of  the  Alimentary  Contents.  The  Faeces. 
— The  alimentary  contents  differ  markedly  in  general  appear- 
ance and  chemical  composition  in  the  various  portions  of  the 
alimentary  tract.  The  reasons  for  this  are  readily  ap- 
parent. Not  only  does  the  food  of  different  animals  differ, 
but  it  is  not  always  the  same  in  the  same  animal.  In  its 
passage  from  the  mouth  to  the  anus  it  is  acted  upon  by  the 
various  portions  of  the  canal  through  which  it  passes,  and 
changes  are  wrought  in  it  of  a  mechanical  and  chemical  char- 
acter. Not  only  is  its  physical  state  of  aggregation  pro- 
gressively altered  in  this  way,  but  it  has  poured  out  upon  it, 
one  after  the  other,  a  number  of  secretions,  each  of  which,  by 
virtue  of  the  substances  contained  in  it;  alters  the  chemical 
composition  of  the  alimentary  contents.  The  metabolic 
products  excreted  by  the  bacteria  accomplish  a  similar  end. 
To  the  changes  brought  about  in  this  way  must  be  added 
those  induced  through  the  absorption  from  the  alimentary 
contents  of  certain  of  the  substances  contained  in  them. 
All  these  are  together  responsible  for  the  progressive  change 
which  the  food  suffers  in  its  passage  from  the  mouth  to  the 
anus. 

The  food  enters  the  mouth  in  a  state  of  coarse  division, 


318  PHYSIOLOGY  OF  ALIMENTATION. 

and  through  the  action  of  the  teeth  is  more  finely  divided. 
With  most  individuals  the  food  as  it  slips  into  the  stomach 
still  contains  large  masses  of  undivided  food,  made  up  more 
particularly  of  pieces  of  meat  and  smaller  but  still  coarse 
pieces  of  boiled  potato,  bread,  etc.  The  mechanical  action 
of  the  stomach,  together  with  the  action  of  the  large  quanti- 
ties of  gastric  juice  poured  out  under  physiological  condi- 
tions upon  the  food  in  this  locality,  serves  to  change  even 
the  external  appearance  of  the  mixed  food.  Not  only  are 
the  larger  pieces  of  starchy  food  broken  into  smaller  ones 
through  the  muscular  contractions  passing  over  the  stomach, 
but  pieces  of  swallowed  meat  suffer  similar  changes  in  their 
state  of  aggregation.  The  connective  tissue  found  in  them 
is  acted  upon  by  the  gastric  juice  and  the  cellular  elements 
in  consequence  are  allowed  to  fall  apart.  Fatty  tissues  suffer 
a  similar  change,  and  the  fat  contained  within  the  cells 
becomes  free.  If  any  fats  have  been  consumed  which  at 
ordinary  temperatures  are  solid,  but  melt  at  body  temper- 
atures, these  melt.  The  formation  of  peptones  from  the 
protein  of  the  meal  imparts  to  the  gastric  contents  a  bitter 
taste. 

The  acid,  liquid,  partially  digested  gastric  contents  pass 
over  in  small  amounts  into  the  duodenum.  Here  they  have 
poured  out  upon  them,  as  soon  as  they  pass  the  pancreatic 
duct,  the  bile  and  pancreatic  juice.  The  color  of  the  bile  im- 
parts itself  to  the  alimentary  contents,  and  the  alkaline  reac- 
tion of  the  pancreatic  juice  reduces  the  acidity  of  the  food  as 
it  has  escaped  from  the  stomach.  Throughout  the  small  in- 
testine the  food  exists  only  as  a  sticky,  mucinous,  brownish- 
yellow  mass  which  adheres  more  or  less  closely  to  the  mucous 
membrane  of  the  alimentary  tract.  The  viscosity  of  this 
mass  increases  gradually  from  above  downward,  and  no- 
where throughout  the  small  or  large  intestine  do  the  alimen- 
tary contents  show  to  the  naked  eye  any  of  the  character- 
istics of  the  food  originally  consumed  by  the  individual. 
These  are  quite  effectually  lost  even  in  the  stomach  after 


ALIMENTARY  TRACT  AS  AN  EXCRETORY  SYSTEM.      319 

digestion  has  gone  on  for  two  or  three  hours.  The  yellowish- 
brown  contents  of  the  small  intestine  assume  a  somewhat 
darker  color  when  the  ileocecal  valve  is  passed,  and  from 
here  down  to  the  anus  the  alimentary  contents  lose  water, 
and  in  consequence  increase  in  consistency  very  rapidly. 
Semisolid  scybala  begin  to  appear  in  the  transverse  and 
descending  portions  of  the  large  intestine,  and  in  the  lower- 
most portions  of  the  large  bowel  the  faeces  proper  are  formed. 
Throughout  the  small  intestine  the  alimentary  contents  have 
no  faecal  odor  under  ordinary  circumstances.  This  is  de- 
veloped after  the  ileoccccal  valve  is  passed. 

The  question  of  the  reaction  of  the  gastro-intestinal  contents 
has  within  the  last  few  years  come  up  again  for  discussion. 
In  consequence  of  more  careful  analyses,  made  possible  through 
advances  in  our  knowledge  of  indicators,  some  of  our  older 
ideas  regarding  the  reaction  of  the  intestinal  contents  will 
have  to  be  set  aside  and  newer  ones  adopted.  The  reaction 
of  the  gastric  contents  after  these  have  remained  in  the  stomach 
for  some  time  is,  under  normal  circumstances,  acid,  and  this 
fact  has  never  been  disputed  since  the  middle  of  the  last  cen- 
tury. Broadly  speaking,  the  contents  of  the  small  intestine 
have  always  been  considered  alkaline.  Except  for  the  first 
few  inches  of  duodenum  in  which  the  fresh  acid  gastric  con- 
tents may  be  found,  the  contents  of  the  remaining  portion  of 
the  alimentary  tract  were  considered  alkaline  in  reaction, 
because  they  had  poured  out  upon  them  the  "pronouncedly 
alkaline"  secretions  of  the  pancreas,  liver,  and  intestine 
itself.  Neglecting  for  the  time  being  the  reaction  of  these 
juices,  let  us  ask  what  means  were  employed  to  ascertain  the 
reaction  of  the  gastro-intestinal  contents?  For  the  most 
part  only  one  indicator  was  used  to  determine  their  acidity 
or  alkalinity,  litmus,  and  this  in  its  poorest  form,  as  litmus 
paper.  Litmus  in  any  form,  however,  is  an  exceedingly 
fallacious  indicator,  at  times  even  useless,  in  solutions  in 
which  carbonates  are  present,  for  litmus  is  not  sufficiently 
sensitive   toward   carlonates.     For  this   reason  litmus  may 


320  PHYSIOLOGY  OF  ALIMENTATION. 

even  show  an  alkaline  reaction  in  solutions  which  are  really 
neutral  or  even  acid. 

A  number  of  authors  have  in  recent  years  employed  in- 
dicators other  than  litmus  (such  as  lacmoid,  phenolphthalein, 
methyl  orange,  alkanna,  rosolic  acid,  alizarin,  curcuma  and 
trapsBolin)  to  ascertain  the  reaction  of  the  intestinal  con- 
tents. Munk,1  who  experimented  in  this  way  on  dogs  and 
hogs  fed  on  various  diets  after  a  period  of  fasting — diets 
predominantly  protein,  or  protein  and  fatty,  or  mixed  in 
character — comes  to  the  following  conclusions:  The  con- 
tents of  the  duodenum,  jejunum,  or  ileum,  in  carnivorous  as 
well  as  in  omnivorous  animals,  no  matter  how  fed,  at  no  time 
show  an  alkaline  reaction,  if  only  indicators  sufficiently  sensi- 
tive to  indicate  the  presence  of  carbonates  and  fatty  acids  be 
employed.  On  a  pure  meat  diet  the  duodenal  and  upper 
jejunal  contents  are  distinctly  even  though  only  faintly 
acid.  Beyond  this  point  and  to  the  ileocsecal  valve  the 
intestinal  contents  are  neither  definitely  acid  nor  alkaline, 
and  may,  in  consequence,  be  considered  neutral.  As  soon  as 
fat  is  added  to  the  diet,  that  is,  protein  and  fat  are  fed  to- 
gether, the  contents  of  the  entire  small  intestine  show  an 
acid  reaction,  attributable,  no  doubt,  in  the  main  to  the 
presence  of  free  fatty  acids  formed  through  the  action  of 
lipase  upon  the  neutral  fats.  In  fact,  under  no  circum- 
stances, even  when  large  amounts  of  carbohydrates  are  given 
together  with  protein,  do  the  contents  of  the  jejunum  or  ileum 
ever  show  an  alkaline  reaction. 

The  experimental  observations  of  Munk  are  corroborated  by 
clinical  findings  on  human  beings.  Macfadyen,  Nencki,  and 
Sieber,2  who  observed  two  cases  of  fistula  of  the  ileum  just 
above  the  ileocsecal  valve,  found  that  the  contents  of  the 
alimentary  tract  when  they  passed  this  point  were  always 
acid  in  reaction  when  the  patients  were  given  a  mixed  diet. 

1  Munk:  Centralblatt  fur  Physiologie,  1902,  XVI,  p.  33. 

2  Macfadyen,  Nencki,  and  Sieber:  Archiv  fur  experimentelle 
Pathologie  und  Pharmakologie,  1891,  XXVIII,  p.  311. 


ALIMENTARY  TRACT  AS  AN  EXCRETORY  SYSTEM.      321 

The  acidity  was  due  to  organic  acids.  These  acids  no  doubt 
inhibit  the  development  of  those  bacteria  which  are  capable 
of  producing  putrefaction  of  the  protein  substances  present 
in  the  small  intestine.  For  this  reason  no  protein  putrefac- 
tion occurs  here  under  normal  circumstances,  or  only  rarely. 

If  what  has  been  said  above  concerning  the  reaction  of 
the  intestinal  contents  is  true,  then  how  are  we  to  reconcile 
it  with  the  observations  that  have  been  made  on  various  fer- 
ments and  their  behavior  toward  acids  and  alkalies?  Alkali- 
proteinase,  for  example,  is  generally  stated  to  act  best  in  an 
alkaline  medium.  In  the  body  of  various  animals,  including 
man,  this  ferment  must  however  work  for  the  most  part  in 
an  acid,  at  the  best  in  a  neutral  medium.  Evidently,  there- 
fore, alkali-proteinase  does  not  work  under  the  most  favorable 
conditions,  so  far  as  reaction  of  surrounding  medium  is  con- 
cerned, in  the  body;  or  else  the  statements  of  the  various 
students  of  the  effect  of  acids  and  alkalies  on  alkali-proteinase 
must  be  revised.  So  far  as  the  former  of  thtse  possibilities  is 
concerned,  we  know  that  alkali-proteinase  will  act  in  neutral 
or  acid  media,  even  very  powerfully  in  neutral  media.  So  far 
as  the  latter  possibility  is  concerned,  it  is  entirely  probable 
that  the  use  of  indicators  better  adapted  to  the  investigation 
of  the  problem  will  show  that  the  alkalinity  in  which  al- 
kali-proteinase acts  best  is  lower  than  we  formerly  supposed, 
and  that  some  of  the  solutions  in  which  alkali-proteinase  is 
known  to  act  very  well  and  which  are  ordinarily  stated  to 
be  alkaline  are  really  neutral  or  even  acid  in  reaction.  Under 
normal  circumstances,  therefore,  alkali-proteinase  may  still 
be  considered  as  acting  in  the  intestine  under  only  slightly 
unfavorable  circumstances. 

What  has  been  said  of  alkali-proteinase  holds  also  for  the 
other  enzymes.  Unquestionably  the  acid  reaction  of  the 
intestinal  contents  may  be  of  service  t'>  certain  of  the  fer- 
ments, such,  for  example,  as  the  acid-proteinase  of  the 
stomach  and  duodenum.  Finally,  even  if  the  acid  reaction 
of   the  contents  of    the  small  intestine   reduces  the  activity 


322  PHYSIOLOGY  OF  ALIMENTATION 

of  the  digestive  ferments  found  here,  it  reduces  still  more 
markedly  that  of  the  ferments  found  in  the  bacteria,  for  the 
growth  of  these  is  decidedly  kept  in  check  throughout  this 
hollow  viscus,  and  their  putrefactive  action  upon  the  food 
(which,  under  pathological  conditions,  may  become  of  a 
serious  character)  prevented  to  a  large  extent. 

The  amount  of  faeces  cast  off  by  an  animal  is  depend- 
ent upon  the  amount  and  character  of  the  food  consumed. 
Other  things  being  equal,  a  large  amount  of  food  will  yield  a 
greater  amount  of  excremehtitious  material  than  a  smaller  one. 
The  extent  to  which  a  food  can  be  absorbed  is  however  of 
great  importance.  Fine  white-flour  breads  are,  for  example, 
absorbed  more  perfectly  than  rye  or  whole-wheat  breads, 
because  they  represent  more  nearly  pure  starch  in  a  form  that 
can  be  acted  upon  by  the  digestive  ferments.  Mashed  potatoes 
yield  less  faecal  matter  than  boiled  potatoes,  for  in  the  former 
the  cellulose  membranes  surrounding  the  cells  are  more  per- 
fectly broken  than  in  the  latter,  and  the  starch  absorption  is 
in  consequence  more  perfect.  Because  of  the  large  amount 
of  cellulose  they  contain,  the  vegetable  diets  in  general  yield 
a  larger  amount  of  faecal  matter  than  meat  diets.  The  faeces 
do  not,  however,  represent  only  remnants  of  food  that  can- 
not be  digested,  but  also  a  certain  amount  that  can  be,  but, 
for  various  reasons,  has  not  been  digested.  In  addition  it 
must  not  be  forgotten  that  the  secretions  of  the  gastro- 
intestinal tract  itself  and  of  the  glands  connected  with  it 
contribute  largely  toward  making  up  the  body  of  the  faeces. 

The  color  of  the  faeces  is  variable.  A  meat  diet  yields 
dark,  one  of  bread,  lighter  faeces.  The  color  is  determined  in 
large  part  by  the  bile,  being  gray  in  its  absence,  yellowish  or 
yellowish  brown  in  its  presence.  For  the  most  part,  it  is  not 
the  bile  pigments  themselves  that  give  this  color,  but  certain 
of  their  derivatives  formed  after  the  bile  has  escaped  into  the 
intestine. 


INDEX  OF  AUTHORS. 

Wherever  subjects  are  presented  at  greater  length  it  is  indicated  by  bold- 
faced type. 


Abderhalden,  on  acid-proteinase,  121;  on  peptides-,  124;  on 
proteolysis,  126;  on  failure  of  tissues  to  digest  themselves, 
140;  on  protein  synthesis,  141;  on  intestinal  fermentation, 
174;  on  duodenal  juice,  245;  on  protein  absorption,  305, 
306,  307 

Abelmann,  on  fat  absorption,  297 

Albertoni,  on  absorption  of  sugars,  285 

Armstrong,  on  lactase,  157 

Arrhenius,  on  electrolytic  dissociation,  260 

Bathazard,  on  movements  of  stomach,  7,  8 

Bauer,  on  protein  absorption,  299 

Bayliss,  on  intestinal  movements,  44;  on  secretin,  77,  212,  22S 
229,  248 ;  on  secretin  and  biliary  secretion,  238 

Beaumont,  8;  on  the  stomach,  188 

Beciiamp,  on  maltase,  105 

Beokek,  on  pancreatic  secretion,  224 

Beijerinck,  on  maltase,  105 

Bence-Jones,  149 

Bernard,  Claude,  on  gastric  juice,  67;  on  alkali-proteinase, 
122;  on  intestinal  tract,  136;  on  urea,  159;  on  saliva, 
179;  on  paralytic  salivary  secretion,  L82;  on  medulla  and 
salivary  secretion,  184;  on  pancreatic  fistula.',  215;  on  bile, 
238;  on  urea  in  alimentary  tract,  315 

v.  Berneck,  on  inorganic  ferments,  94 

Bernstein,  on  inhibition  of  pancreas,  222 

323 


324  INDEX  OF  AUTHORS. 

Berreswil,  on  gastric  juice,  67 

Beyerinck,  on  lactase,  157 

Bidder,  on  saliva,  64;  on  gastric  secretion,  200,  204 

Billitzer,  on  inorganic  ferments,  94 

Boas,  on  emptying  of  stomach,  16 

Bock,  on  diabetes,  315 

Bredig,  on  inorganic  ferments,  94,  95 

Brinck,  on  Micrococcus  restituens,  307 

Brotzu,  on  alimentary  bacteria,  161 

Brown,  on  maltase,  105 

Brucke,  on  acid-pro teinase,  114;  on  swelling  of  fibrin,  118;  on 

protein  absorption,  299 
Bruno,  119;  on  bile,  237,  239 
Brunton,  on  acid-proteinase,  115 
Bucheler,  103,  106,  155 
Buchner,  on  zymase,  81;   on  acid-proteinase,  119 

Cannon,  on  deglutition,  4,  5,  6 ;  on  salivary  digestion  in  stom- 
ach, 15,  104;  on  pylorus,  16,  17,  20;  on  gastro-intestinal 
movements,  7,  8,  12,  15,  22,  43,  44,  46 

Chigin,  on  gastric  fistulse,  189;  on  gastric  secretion,  192,  193, 
198,  205,  210;  on  adaptation  of  digestive  glands,  234 

Cohen,  79,  87,  89,  107 

Cohnheim,  on  protease,  75,  146;  on  amylase,  99;  on  absorp- 
tion, 279,  280 

Colin,  on  saliva,  186 

Connstein,  on  fat  absorption,  289 

Conradi,  on  curdling  of  milk,  112 

Cremer,  on  glycogen,  103 

Czerny,  on  protein  absorption,  299 ;  on  removal  of  stomach,  302 

Dakin,  on  arginase,  76,  158,  308 

Dastre,  on  bile,  238,  239 

Day,  on  salivary  digestion  in  stomach,  15 

Delezenne,  on   pancreatic  proferments,  70;   on  enterokinase, 

246;  on  pancreatic  secretin,  248 
Denathe,  on  sucrase,  154 
Deucher,  on  protein  absorption,  304 
Dolinski,  on  pancreatic  secretion,  224,  225 


INDEX  OF  AUTHORS.  325 

Dominici,  on  alimentary  bacteria,  162 

Duclai  \,  on  sucrase,  154;  on  alimentary  bacteria,  166 

Edkins,  on  acid-proteinase,  109;  on  gastric  secretion,  212 
EPPRONT,  103,  106,   1")");    on  sucrase,   L56 
ElJKMANN,  on  diffusion  of  colloids,  L'SS 

Ernst,  on  colloidal  platinum,  96 

Eschbrich,   on  alimentary   bacteria,    161,   164;  on  B.   lastis 

aerogenes,  163 
Esselmont,  on  intestinal  movements,  46 
Ewald,  on  emptying  of  stomach,  1G 

Faber,  on  gastric  elimination,  312 

Fischer,  Emil,  on  acid-proteinase,  121;  on  peptides,  124;  on 
protein  synthesis,  140;   on  lactase,  157 

Fischer,  Martin  H.,  79,  87,  89,  107 ;  on  diabetes,  315 

Flexner,  on  toxin  excretion,  317 

Fodera,  on  pancreatic  fistula?,  216 

Friedenthal,  on  acid-proteinase,  115;  on  absorption  of  col- 
loids, 288 

Friedlander,  on  absorption  of  acid-albumin,  299 

Frouin,  on  pancreatic  proferments,  70;   on  enterokinase,  246 

Fubini,  on  intestinal  movement,  46 

C.erhardt,  on  aliment ary  bacteria,  161 
Gilbert,  on  alimentary  bacteria,  162 
Ginsberg,  on  carbohydrate  absorption,  280 
Glaessner,  on  pancreatic  juice,  69;  on  human  pancreatic  secre- 
tion, 226,  227,  •_,.!,.>;   on  bile,  239 
(Ii.iwsm,  on  salivary  fistula?,  177 
Gmelin,  on  gastric  juice,  07 
(  iB  \n  \M.  on  colloid-,  '_'.")! 

Grutzner,  on  movements  of  intestine,  22;  on  estimation  of 
proteolysis,  130 

Gl  MILEWSKI,  on  saline  cathartics,    IS 

IlxMi.i  RQER,  on  human  intestinal  juice,  71.  75,  76,  77 

Hammarsten,  on  bile,  72 ;  on  caseinase,  110;  on  casein,  Hi;  on 
calcium  and  milk,  112;  on  acid-proteinase,  118 


326  INDEX  OF  AUTHORS. 

Hanford,  on  alimentary  elimination,  312 

Hanriot,  on  reversible  action  of  lipase,  151,  153;  on  mechan- 
ism of  fat  absorption,  289 

Harley,  on  pancreas,  304 

Hedon,  on  fat  absorption,  297 

Heidenhain,  on  gastric  juice,  67;  on  gastric  fistulse,  189,  215, 
246;  on  gastric  secretion,  210;  on  bile,  239;  on  absorption, 
280 

Hekma,  on  human  intestinal  juice,  74,  75,  76,  77 

Heron,  on  maltase,  105 

Herzog,  on  caseinase,  110;  on  protein  synthesis,  143 

Hewlett,  on  action  of  bile,  240 

Hill,  on  reversible  action  of  maltase,  106 

Hirsch,  8;  on  the  pylorus,  12,  16,  20 

Hober,  on  molecular  weight  and  osmotic  pressure,  253;  on 
absorption  of  salts,  276 

Hoffmann,  on  diabetes,  315 

Hofmeister,  8;  on  catharsis,  50;  on  peptones,  146;  on  gela- 
tine plates,  267;  on  assimilation  of  carbohydrates,  284 

Hoppe-Seyler,  on  saliva,  62 

Ikeda,  on  inorganic  ferments,  94 

Jones,  on  tubercle  bacilli,  162 
Jurgens,  on  gastric  secretion,  200 

Kanitz,  on  alkali-proteinase,  123 

Kastle,  on  lipase,  75;   on  reversible  action  of  lipase,  151;  on 

mechanism  of  fat  absorption,  289 
Ketscher,  on  gastric  secretion,  202 
Kjeldahl,  on  amylase,  103;  on  sucrase,  156 
Kladnizki,  on  bile,  237 
Klein,  on  alimentary  bacteria,  162 
Klemensiewicz,  on  gastric  juice,  189 
Kleyn,  on  alimentary  bacteria,  162 
Kohlbrtjgge,  on  alimentary  bacteria,  161,  164 
Konowaloff,  on  gastric  juice,  66 
Kossel,  on  arginase,  76,  158,  308 
Kotljar,  on  appetite  juice,  205 


INDEX  OF  AUTHORS.  327 

Kovesi,  on  absorption  of  salts,  276 

Kroeber,  on  maltose,  100 

Kronecker,  on  deglutition,  !,  5,  0 

KuDREWETZKY,  oil  nerve  supply  of  pancreas,  223 

Kuhne,  on  enzymes,  SI ;  on  peptones,  121,  124,  148 

Kulz,  on  diabetes,  315 

Kunkel,  on  gastric  elimination,  311 

Kutscher,  on  protein  absorption,  301 

Kuwsciiinski,  on  pancreatic  secretion,  225 

Labord,  on  acid-proteinase,  119 

Langley,  on  acid-proteinase,  119;   on  salivary  secretion,  179, 

180 
Langstein,  on  acid-proteinase,  121 
Latschenberger,  on  protein  absorption,  299 
Lawrow,  on  acid-proteinase,  121 
Lepage,  on  nervous  control  of  pancreas,  228 
Lintner,  on  maltase,  106 
Lintwarew,  on  closure  of  pylorus,  21 
Lobassoff,  on  appetite  juice,  205,  208;  on  oils,  211 
Loeb,  on  muscle  and  nerves,  49 
Loevenhart,  on  lipase,  75,  151;  on  curdling  of  milk,  112;  on 

mechanism  of  fat  absorption,  2S9,  291 
Ludwig,  on  salivary  secretion,  181,  187;  on  pancreatic  fistula?, 

215;  on  protein  absorption,  302 

MacCallum,  on  saline  cathartics,  46;   on  alimentary  excretion, 

314,  315,  316 
Macfadyen,  on  alimentary  contents,  320 
Malfetti,  on  acid-proteinase,  121 
Mall,  on  intestinal  movement,  27,  43 
Manning,  on  human  intestinal  juice,  74 
Martin,  on  bile,  239 
Mathews,  on  salivary  secretion,  1S2 
Mays,  on  preparation  of  alkali-proteinase,  122 
McIntosh,  on  inorganic  ferments,  94 
Meltzer,  on  deglutition,  4,  5,  6 
Mendel,  on  paralytic  secretion  of  intestine,  244;    on  protein 

absorption,  302;  on  alimentary  excretion.  :;i  l,  312,  313 


328  INDEX  OF  AUTHORS. 

v.  Mering,  on  carbohydrate  absorption,  286 

Mester,  on  intestinal  fermentation,  165 

Mett,  on  estimation  of  proteolysis,  130 

Meyer,  on  lipoids,  267,  269 

Miller,  on  alimentary  bacteria,  163 

Minkowski,  on  fat  absorption,  297 

Mitscherlich,  on  saliva,  62 

Miyamota,  on  acid-proteinase,  115 

Moore,  on  saliva,  63;   on  sulphocyanate,  65;   on  gastric  juice* 

67;   on  fatty  acids,  241;   on  solubility  of  fatty  acids,  291, 

297 
Moore,  Gertrude,  on  alterable  permeability  of  intestine,  280} 

on  alimentary  excretion  of  sugar,  316 
Moser,  on  deglutition,  4,  5,  6 
MtJLLER,  Friedrich,  262 ;  on  fat  absorption,  295 
Munk,  on  reaction  of  saliva,  64;   on  carbohydrate  absorption, 

286;  on  fat  absorption,  291,  294,  295,  296,  297;  on  protein 

absorption,  299,  302;   on  reaction  of  alimentary  contents, 

320 
Musculus,  on  starch  digestion,  102 

Nagano,  on  human  intestinal  juice,  74,  76;    on  absorption  of 

sugars,  285 
Nencki,  on  acid-proteinase,  115;  on  intestinal  contents,  320 
Neumeister,  on  peptones,  146;  on  protein  absorption,  299 
Nielson,  on  inorganic  ferments,  94,  97 
Nirenstein,  119 
Nuttall,  on  intestinal  flora,  174 

Ogata,  on  protein  absorption,  302 

Ohl,  on  saliva,  62,  63 

Okotjneff,  on  protein  synthesis,  143 

Oppler,  on  intestinal  fermentation,  165 

Osborne,  113 

Ostwald,  79;  viscosimeter,  131;  on  mechanical  affinity,  250 

O 'Sullivan,  on  catalysis,  155 

Overton,  on  lipoids,  267,  269,  271,  272 

Pauli,  on  colloids,  182 

Pavy,  on  non-digestion  of  stomach,  136 


INDEX   OF   AUTHORS.  329 

Pawi.ow,  on  gastric  juice,  66,  1  L9;  on  salivary  fistula,  177;  on 
saliva,  184;  on  gastric  fistulae,  189;  on  cesophagotomy,  191; 
on  gastric  secretion,  192,  L93,  194,  L95,  199,  200,  202;  on 
appetite,  203,  207,  209;  on  pancreatic  fistula,  215;  on 
pancreatic  juice,  221,  222;  on  bitters,  231;  on  adaptation 
of  digestive  glands,  234;  on  intestinal  secretion,  243;  on 
enterokinasc,  246,  247 

Pbkelhaking,  on  acid-proteinase,  115 

Penzoldt,  on  emptying  of  stomach,  16,  17,  18,  19;  on  ali- 
mentary elimination,  311 

Pfaundler,  on  acid-proteinase,  121 

Pfleiderer,  on  acids  and  acid-proteinase,  116 

Pfluger,  on  intestinal  movements,  43 ;  on  fatty  acids,  241 

Popielski,  on  pancreatic  proferments,  70;  on  nervous  control 
of  pancreas,  228;  on  nerve  supply  of  pancreas,  223 

Popoff,  on  alimentary  bacteria,  161 

Pregl,  on  urea,  315 

Prout,  on  gastric  juice,  67;  on  pancreatic  juice,  68 

Rachford,  on  bile,  239;  on  digestion  of  fat,  288,  290 

Reid,  on  absorption,  280 

Reinders,  on  inorganic  ferments,  94 

Riciiet,  on  gastric  secretion,  200 

Ringer,  on  antagonism  between  sodium  and  calcium,  48 

Rockwood,  on  fatty  acids,  241;  on  solubility  of  fatty  acids, 
291,  297 

Rohmann,  on  saline  cathartics,  48;  on  intestinal  juice,  73;  on 
absorption  of  sugars,  285 

Rona,  on  feeding  of  amino-acids,  307 

Rosenfeld,  on  fat  deposition,  294 

Rosenstein,  on  carbohydrate  absorption,  286;  on  fat  absorp- 
tion, 294,  295;  on  protein  absorption,  302 

ROSSBACH,  8 

Roux,  on  movements  of  stomach,  7,  8 

Salaskin,  on  acid-proteinase,  121 
Salkowski,  on  alkali-proteinase,  122 
S.\i.\  kh.1,  mi  peptones,  l  16 
Samuely,  on  protein  absorption,  305,  306 


330  INDEX  OF  AUTHORS. 

Sandmeyer,  on  fat  absorption,  298 

Schepowalniko  w,  on  fat  digestion,  239 ;  on  enterokinase,  246 

Schiff,  119 

Schild,  on  alimentary  bacteria,  161 

Schmidt,  on  saliva,  64;  on  gastric  juice,  67,  200,  204 

Schmidt-Mulheim,  on  protein  absorption,  302 

Schonbein,  on  inorganic  ferments,  94 

Schottelius,  on  alimentary  flora,  175 

Schumow-Simanowski,  on  gastric  juice,  66;  on  cesophagotomy, 
191;  on  gastric  secretion,  192;  on  nervous  control  of  gas- 
tric secretion,  200,  202 

Schtjtz,  8;   on  ferments,  131 

Seemann,  on  protein  absorption,  301 

Seifert,  on  intestinal  fermentation,  165 

Serdjukow,  on  pylorus,  16,  20 

Shiga,  bacillus  of,  317 

Sieber,  on  acid-proteinase,  115;  on  intestinal  contents,  320 

Spiess,  on  salivary  secretion,  181 

Spiro,  on  colloids,  269 

Spriggs,  on  estimation  of  proteolysis,  131,  144 

Ssanozki,  on  gastric  secretion,  200,  205 

Starling,  on  movements  of  intestine,  22 ;  on  nervous  control  of 
alimentary  tract,  41 ;  on  pancreatic  secretin,  77,  248 ;  on 
secretin,  212,  228,  229;  on  secretin  and  biliary  secretion, 
238;  on  absorption,  276 

St.  Martin,  Alexis,  188 

Sucksdorff,  on  alimentary  bacteria,  161,  162 

Talma,  on  antiseptic  action  of  bile,  166 

Tammann,  88 

Taylor,  on  lipase,  151,  153 

Thacher,  on  alimentary  elimination,  311,  312,  313 

Thierfelder,  on  intestinal  flora,  174 

Thiry,  on  intestinal  juice,  73 ;  on  intestinal  fistulse,  243 

Thompson,  119,  189,  200,  209,  215,  217,  221,  224,  225,  231,  237 

Tiedemann,  on  gastric  juice,  67 

Tompson,  on  catalysis,  155 

Tubby,  on  human  intestinal  juice,  74 

Uschakoff,  on  gastric  secretion,  203 


INDEX  OF  AUTHORS.  331 

van't  Hoff,  laws  of,  259,  260 

Vella,  on  intestinal  juice,  73;   on  intestinal  fistula,  243 

Vernon,  on  protease,  149;   on  lactase,  236 

Ville,  on  fat  absorption,  297 

Voit,  on  protein  absorption,  299 

von  Bekneck,  on  inorganic  ferments,  94 

von  Merino,  on  carbohydrate  absorption,  286 

Walther,  on  pancreatic  secretion,  217,  225;  on  pancreatic 
juice,  220;  on  adaptation  of  digestive  glands,  234 

Weinland,  on  pancreatic  amylase,  91;  on  antiproteinase,  65, 
133,  144;  on  failure  of  autodigestion  of  alimentary  tract, 
135;  on  intestinal  ulcers,  139;  on  lactase,  157;  on  adapta- 
tion of  glands  to  food,  234,  236 

Wertheimer,  on  nervous  control  of  pancreas,  22S 

\\  kstphalen,  on  bile,  71 

Wherry,  on  cholera,  167 

Williams,  on  bile,  239 

Wroblewski,  on  acid-proteinase,  119 

Zunz,  on  acid-proteinase,  121 


INDEX  OF  SUBJECTS. 


Wherever  subjects  are  presented  at  greater  length   it  is  indicated  by  bold- 
faced type. 


Absorption,  249;  problem  of,  249;  nature  of  substances  con- 
cerned in,  250;  forces  active  in,  250,  2.">7;  role  of  osmotic 
pressure  in,  262,  263,  264,  265;  role  of  colloids  in,  267;  of 
salts,  274  (see  also  Salts);  of  water,  2(52  269;  of  carbo- 
hydrates, 2S2  (see  also  Carbohydrates);  of  fats,  287  (see 
also  Fats);  of  proteins,  299  (see  also  Proteins);  of  lipoid- 
soluble  substances,  268,  278,  279;  effect  of  chemicals  on, 
280 

Absorptive  system,  alimentary  tract  as,  249 

Acetic  acid,  106 

Acid-proteinase,  114;  distribution  of,  114;  in  stomach,  67,  114; 
preparation  of,  114;  chemical  character  of,  115;  effect  of 
acids  on,  116;  effect  of  chemical  substances  on,  118;  effect 
of  temperature  on,  120;  action  of,  on  fibrin,  120;  products 
of  digestion  by,  121  ;  compared  with  alkali-proteinase,  122; 
role  of,  in  protein  absorption,  300,  301 

Acids,  as  electrolytes,  260;  organic,  of  alimentary  contents,  321 

Adaptation  of  digestive  glands  to  food,  234;  mechanism  of,  236 

Affinity,  mechanical,  250 

Alcohol,  ethj  I.  L06 

Alcohols,  diffusion  of,  into  protoplasm,  271 ;  absorption  of,  by 
alimentary  tract ,  27S,  L'79 

ALDEHYDES,  diffusion  of,  int..  protoplasm,  271 

Alc-e,  behavior  of,  in  various  solutions,  270,  271 

333 


334  INDEX  OF  SUBJECTS. 

Alimentary  contents,  character  of,  317;  progressive  changes 
in,  317;  reaction  of,  319,  320;  effect  of,  on  alimentary  fer- 
ments, 321,  322 

Alimentary  tract,  general  functions  of,  1 ;  movements  of  food 
through,  36;  nervous  control  of,  41;  effect  of  emotion  on 
movements  of,  44,  45,  46;  failure  to  digest  itself,  135,  140; 
bacteria  of  (see  Bacteria) ;  physiological  connection  between 
different  portions  of,  248;  as  absorptive  system,  249;  as 
excretory  system,  311;  predominant  permeability  of,  in 
one  direction,  279,  280 

Alkali-proteinase,  of  pancreas,  69;  preparation  of,  122; 
effect  of  medium  on,  123;  effect  of  temperature  on,  123; 
effect  of  concentration  of  ferment  on,  124 ;  cleavage  of  pro- 
teins by,  124;  end  products  of  digestion  by,  125;  and  bile, 
241 ;  role  of,  in  protein  absorption,  300,  301 

Alkalies  and  gastric  secretion,  232 

Amino-acids,  121,  124,  126;  in  intestinal  contents,  301 

Amphoproteinase,  129 

Amylase,  99;  of  saliva,  62,  65;  of  pancreas,  69;  of  intestine, 
75 ;  sources  of,  99 ;  salivary  and  pancreatic  compared,  100 ; 
effect  of  external  conditions  on,  100;  action  of,  on  starch, 
101;  effect  of  temperature  on,  103;  possible  reversible 
action  of,  103;  and  glycogen.  103;  separation  from  mal- 
tase,  105 ;  and  bile,  241 

Amylopsin  (see  Amylase) 

Anacidity,  consequences  of,  in  stomach,  165  -^,, 

Animal  membranes  (see  Membranes) 

Antiferment,  80,  133  (see  also  Antiproteinase) 

Antipepsin  (see  Antiproteinase) 

Antiproteinase,  of  stomach,  68;  of  intestine,  96,  133;  prep- 
aration of,  133;  action  of,  134;  effect  of  heat  on,  134; 
general  distribution  of,  137 ;  consequences  of  lack  of,  137    i 

Antitoxins,  139 

Antitrypsin  (see  Antiproteinase) 

Appetite,  203;  as  gastric  excitant,  203;  physiological  impor- 
tance of,  230 

Appetite  juice,  204,  205;  physiological  importance  of,  205 

Arginase,  of  intestine,  76;   and  arginin,  158,  308 

Arginin,  digestion  of,  76;   and  arginase,  158 


i\i>i:x  OP  subjects.  335 

Absbnic,  elimination  of,  through  s\ ach,  311 

Asi'vms,  133  (see  also  A.ntipmh  inase) 
Ask,  in  naming  ferments,  82 

Assimii.  \  riox  limits  of  carbohydrates,  I'M,  l_',S.~> 

Bacillus,  coli  communis,  164;  putrificus,  164;  subtilis,  164; 
acidophilus,  164 

Bactkkia  of  VLIMENTARY  TRACT,  160;  existence  of,  161  j  num- 
ber of,  Kii  ;  weight  of,  162;  kinds  of ,  162;  distribution  of, 
165;  destruction  of,  in  stomach,  165;  destruction  of,  in 
intestine,  166;  products  of,   168 

Bacterium,  lactis  aerogenes,  163 

BARIUM,  alimentary  excretion  of,  313 

Bases,  as  electrolytes,  260 

Bence-Jones  PROTEIN,   1  111 

Bile,  70;  amount  of,  71;  physical  character  oF,  71;  chemical 
composition  of,  72;  secretion  of  (see  Biliary  secretion); 
functions  and  physiological  importance  of,  237,  23S;  and 
digestion  of  fats,  238,  239,  240,  241 ;  as  adjuvant  to  pan- 
creatic ferments,  241;  as  solvent  for  fatty  acids,  241;  as 
inhibitor  of  gastric  digestion,  242;  antiseptic  action  of,  242; 
as  aid  to  peristalsis,  242;  as  activator  of  proferments,  242; 
role  of,  in  fat  absorption,  296,  297,  298 

Bile  acids.  72 

Bile  pigments,  72 

BlLIARY  secretion,  237;  into  intestine,  237;  in  relation  to 
feeding,  237;  effect  of  foods  on,  238;  mechanism  of,  238; 
and  pancreatic  secretin,  238 

Bismuth  subnitrate,  and  study  of  gastro-intestinal  move- 
ments, 7 

Bitters,  231 

Br  ret  test,  and  peptides,  128,  1  12 

Blood,  pressure  of,  and  salivary  secretion,  187;  red  corpuscles 
of,  256;  constancy  of  protein  composition  of,  305,  306 

Bread,  and  gastric  secretion,  198;  and  pancreatic  secretion,  220 

Bin  wkk's  islands,  secretion  of,  245 

Calch  m,  antagonistic  action  of,  toward  sodium,  is 
CalCI  i.i,  salivary,  65 


336  INDEX  OF  SUBJECTS. 

Cane-sugar  (see  Sucrose) 

Capillary  forces,  250 

Carbohydrates,  rate  of  leaving  stomach,  17;  absorption  of, 
282,  286  (see  also  Absorption);  found  in  the  food,  282; 
form  of  absorption  of,  283 ;  action  of  enzymes  on,  283,  284 ; 
assimilation  limits  of,  284,  285 

Casein,  111 

Caseinase,  of  stomach,  67;  of  pancreas,  69;  properties  of,  110; 
coexistence  with  proteolytic  ferments,  110;  preparation  of, 
110;  effect  of  external  conditions  on,  111;  and  antipro- 
teinase,  145 

Catalysis,  79;  rate  of,  85;  effect  of  external  conditions  on,  85; 
effect  of  temperature  on,  87;  effect  of  products  on,  89  (see 
also  Catalyzers) 

Catalytic  agents  (see  Catalyzers) 

Catalyzers,  79;  positive,  79;  negative,  79;  inorganic,  79; 
organic,  80 

Cathartics,  action  of  saline,  46;  increased  peristalsis  through, 
47;  increased  secretion  produced  by,  48;  antagonistic  ac- 
tion of  calcium  on,  48 ;  and  secretion  of  water,  267 

Cell-wall,  morphological,  257 

Centre,  for  oesophageal  movements,  42 ;  for  gastric  movements, 
43 

Cerebrin  as  a  lipoid,  274 

Chemical  equilibrium,  106 

Cholesterin  as  a  lipoid,  274 

Chorda  tympani,  and  salivary  glands,  178 

Chyle,  294 

Cocoa  butter,  deposition  of,  after  feeding,  294 

Coefficient  of  distribution,  272 

Colloidal  solutions  of  noble  metals,  94;  methods  of  pre- 
paring, 94;  effect  of  temperature  on,  95 ;  incompleteness  of 
reactions  catalyzed  by,  97;  reversibility  of  action  of,  97 
(see  also  Colloids) 

Colloids,  251;  affinity  of,  for  water,  250,  251;  amorphous 
character  of,  251;  solutions  of,  252;  osmotic  pressure  of, 
252 ;  typical,  252 ;  molecular  weight  of,  252,  253 ;  diffusion 
of,  253;  and  absorption,  254;  examples  of,  254;  absorption 
of,  288;  diffusion  of  colloids  into,  288,  289 


INDEX  OF  SUBJECTS.  387 

Condiments,  231 

Crystalloids,  251;  crystalline  character  of,  251;  solutions  of, 
'_'.">_';  osmotic  pressure  of,  252;  molecular  weight  of,  252, 
253;  diffusion  of,  253;  and  absorption,  254;  examples  of, 
25  I 

Cul-de-sac,  gastric,  189 

I  Systicerci,  l  ■">•") 

Cytasi:,  170;  ami  cell nlose,  284 

Dead  matter,  L35,  136 

Defecation,  acl  of,  35;  lime  of,  40 

Deglutition,  voluntary  control  of,  4;  involuntary  character  of, 
4;  experimental  observations  on,  4;  muscles  concerned  in, 
4;  of  liquids,  5,  6;  of  solids,  5,6;  in  cats,  5;  in  fowls,  5; 
in  dogs,  6;  in  man,  6;  time  required  for,  6;  nervous  con- 
trol of,  41;   cent  re  for,  41 

Dextrin,  99,  102;   and  maltose,  104 

Dextrose,  and  maltase,  104;  as  chief  sugar  of  the  body,  282, 
283 

Diabetes,  starvation,  2S4,  285;  from  sodium  chloride  injec- 
tions, 315 

Diastase  (see  Anu/lnsr) 

Diet  and  gastric  secretion,  1!»2;  and  pancreatic  secretion,  216 

Diffusion,  250,  257,  25S;  of  colloids  and  crystalloids,  252,  253, 
254,  2."i7,  258;  of  gases,  257;  of  chemicals  into  protoplasm, 
271,  272 

Diffusion  velocity,  of  salts,  276,  277 

Digestive  glands,  adaptation  of,  to  food,  234 

Dissociation,  electrolytic,  260 

Distribution  coefficient,  272 

Duodeni  m.   passage  of  t 1   into,    14;    effect  of  acid  in,  20; 

secretion  of,  245;   ferments  found  in,  245 

1  >i  9ENTER1 ,  Shig  \  bacillus  of,  317 

Electrolyte,  260 

Electrolytic  dissociation,  260 

Emotion,  effect  of,  on  alimentary  movements,  44 

Emi  lsifk  \  1 1"\  of  fats,  240 

Emulsin,  88 


338  INDEX  OF  SUBJECTS. 

Enemas,  fate  of  nutrient,  52 

Enteric  juice  (see  Intestinal  juice) 

Enterokinase,  70,  76,  92,  244,  246;   as  activator  of  ferments, 

246 ;  nature  of,  247 ;  secretion  of,  247 
Enzymes,  81  (see  also  Ferments  and  Catalyzers) 
Epithelium  of  intestine,  selective  permeability  of,  256 
Equilibrium,  chemical,  106 
Erepsin  (see  Protease) 

Erythrite,  diffusion  of,  into  protoplasm,  271 
Esters,  diffusion  of,  into  protoplasm,  271 
Ethyl  acetate,  106 
Ethyl  alcohol,  106 
Ethyl  butyrate,  analysis  and  synthesis  of,  by  platinum,  97; 

analysis  and  synthesis  of,  by  lipase,  151 
Excretion,  as  function  of  alimentary  tract,  311;  urinary  and 

alimentary,  compared,  312,  314 

Faeces,  317;  amount  of,  322;  effect  of  food  on,  322;  color  of, 
322 

Fat,  rate  of  leaving  the  stomach,  17,  21 ;  digestion  of,  75 ;  and 
lipase,  149,  287;  and  gastric  secretion,  239;  emulsification 
of,  240,  287,  288 ;  chemical  changes  in,  after  ingestion,  287, 
291;  analysis  of,  in  intestine,  291,  292;  synthesis  of,  in 
intestine,  293;   absorption  of  (see  Fat  absorption) 

Fat  absorption,  287;  amount  of,  287;  form  in  which  it  occurs* 
and  solubility  of  absorption  products,  288 ;  theories  of,  289, 
290,  291,  292,  293,  294;  paths  of,  294,  295;  after  occlusion 
of  thoracic  duct,  295;  velocity  of,  295;  amount  of,  295; 
role  of  bile  in,  296,  297,  298;  role  of  pancreas  in,  296,  297, 
298  (see  also  Fat  digestion) 

Fat  digestion,  as  influenced  by  bile,  238,  239;  as  influenced  by 
intestinal  and  pancreatic  juices,  239 

Fatty  acids,  solubility  of,  241,  242 

Fermentation,  79;  theories  of,  83;  velocity  of,  85;  effect  of 
hydrocyanic  acid  and  hydrogen  sulphide  on,  98 ;  in  gastro- 
intestinal tract,  165 

Ferments,  inorganic,  79;  organic,  80;  organized,  81;  un- 
organized, 81 ;  nomenclature  of,  81 ;  general  properties  of, 
83,  84;  effect  of  temperature  on,  86;  decomposition  of,  86; 


TXDEX   OF  SUBJECTS.  339 

reversibility  of  action  of,  90;  synthetic  action  of,  90;  ana- 
lytic action  of ,  !)<);  extraction  of,  91 ;  relation  of,  to  pro- 
ferments, 93;  analogy  between  organic  and  inorganic,  97; 

effect  of  poisons  on,  97;  action  of  human,  99 

Ferment  units,  220 

Fistulas,  gastric,  188;  pancreatic,  215;  biliary,  237;  intestinal, 
243;   lymphatic,  286,  294,  :;(>■-• 

Food,  and  gastric  secretion,  192;  and  pancreatic  secretion,  216; 
adaptation  of  digestive  glands  to,  234;  physico-chemical 
classification  of,  250 ;  chemical  classification  of,  250 ;  phys- 
ical character  of,  251 

Gall-bladder,  fistula?  of,  237 

Gall-duct,  fistula  of,  237 

Gas,  diffusion  of,  257,  258 ;  pressure,  258 

Gastric  contents,  318 

Gastric  fistul.e,  188 

Gastric  juice,  60,  188;  amount  of,  in  twenty-four  hours,  66; 
acidity  of,  66;  ferments  of,  67;  hydrochloric  acid  of,  67; 
quantitative  variations  in,  192;  qualitative  variations  in, 
193;  acid  of,  195  (see  also  Gastric  secretion) 

Gastric  secretin,  211  (see  also  Secretin  and  Pancreatic  se- 
cretin) 

Gastric  secretion,  regulation  of,  188;  effect  of  diet  on,  192, 
195;  quantitative  variations  in,  192;  qualitative  variation 
in,  193;  effect  of  different  foods  on,  195;  and  meat,  198- 
and  bread,  198;  and  milk,  198;  relation  of  nervous  system 
to,  200;  excited  by  appetite,  203;  chemical  excitation  of, 
208;  psychic  excitation  of,  203;  and  mechanical  stimula- 
tion, 209,  232;  inhibition  of,  by  sodium  carbonate,  210; 
inhibition  of,  by  oils,  211;  significance  of  physiology  of, 
230;  effect  of,  on  pancreas,  232;  relation  of,  to  other 
organs,  233  (see  also  Gastric  juice) 

Giant  molecule  of  caseinasc  and  proteinase,  110 

Glands  of  Brunner,  secretion  of,  245 

Glucase  (sec  Maltase) 

Glycogen,  91 ;  effect  of  amylase  on,  103 

Gram-molecule,  definition  of,  47 

Hexone  bases.  126 


340  INDEX  OF  SUBJECTS. 

Holothuria  tubulosa,  absorption  in,  280 
Hydrocarbons,  diffusion  of,  into  protoplasm,  271 
Hydrocharis,  plasmolysis  of,  271 
Hydrochloric  acid,  195,  199 
Hydrocyanic  acid  and  fermentation,  98 
Hydrogen  peroxide,  decomposition  of,  94 
Hydrogen  sulphide  and  fermentation,  98 

Icterus,  242 

Ileocecal  valve,  29 

Immunity,  140;  of  tissues  to  ferments,  135 

Indicators,  320 

Indigo  enzyme,  88 

Intestinal  contents,  character  of,  317 

Intestinal  fistula,  243 

Intestinal  juice,  73;  physical  character  of,  73,  244;  human, 
74 ;  ferments  of,  75 ;  antiproteinase  of,  76 ;  enterokinase  of, 
76;   pancreatic  secretin  of,  79 

Intestinal  secretion,  237;  regulation  of,  243  (see  also  Intes- 
tine) 

Intestine,  ulcers  of,  139;  contents  of  large  and  small,  com- 
pared, 318,  319;  importance  of,  in  protein  digestion,  302; 
and  synthesis  of  protein,  306 ;  permeability  of  epithelium  of, 
256,  267 

Intestine,  large,  movements  of,  29;  antiperistalsis  in,  29; 
tonic  constrictions  in,  30 ;  peristaltic  waves  in,  36 ;  passage 
of  food  into,  40;  time  food  spends  in,  40;  effect  of  emo- 
tional states  on  movements  of,  45;  absorption  in,  30,  77; 
secretion  of,  77 ;  enzymes  in,  77 ;  putrefaction  in,  78 

Intestine,  small,  movements  of,  22;  segmenting  movements 
in,  25,  26,  27;  peristaltic  movements  in,  28;  passage  of 
food  into,  39;  nervous  supply  of,  43,  44;  effect  of  emo- 
tional states  on  movements  of ,  45 ;  secretion  from,  243, 244 ; 
relation  of  nervous  system  to  secretion  from,  244,  245; 
paralytic  secretion  of,  244 ;  secretion  into  isolated  loops  of, 
244;  absorption  of  peptones  from,  309,  310 

Invertase  (see  Sucrase) 

Invertin  (see  Sucrase) 

INVERT-SUGAR,  153 


INDEX  OF  SUBJECTS.  341 

Iodides,  elimination  of,  311 

Ionization,  260 

Ions,  260 

isosmotic  solutions,  268 

Isotonic  solutions,  268 

Ketones,  diffusion  of,  into  protoplasm,  271 
Kidneys  and  alimentary  tract  in  excretion,  312 
Kinase,  248 

Lactase,  of  pancreas,  69;  of  intestine,  76,  157;  "reversible  ac- 
tion of,  157;  appearance  of,  in  pancreas,  235;  appearance 
of,  in  small  intestine,  235 

Lactose,  digestion  of,  76;  and  lactase,  157;  adaptation  of 
pancreas  to,  234,  235 

Lanolin,  failure  of  absorption  of,  289 

Large  intestine  (see  Intestine,  large) 

Lecithin,  in  digestion  of  triacetin,  241 ;  as  a  lipoid,  274 

Lipase,  149;  of  stomach,  67,  291 ;  of  pancreas,  69;  of  intestine, 
75;  distribution  of,  150,  291 ;  preparation  of ,  150 ;  effect  of 
external  conditions  on,  150;  reversible  action  of,  151;  and 
bile,  238,  239,  240,  241 ;  destruction  of,  in  stomach,  298 

Lipoidal  absorption,  268;  development  of  conception  of,  268, 
269,  270 

Lipoids,  274;  role  of,  in  absorption,  279 

Living  matter,  135,  136 

Lymphatic  fistula,  Munk  and  Rosenstein's  case  of,  286,  294, 
302 

Maltase,  104;    of  saliva,  62,  65;    of  intestine,  76;    separation 

from  amylase,  105;  sources  of,  105 
Maltose,  99;   digestion  of,  76;  and  maltase    104;  analysis  of, 

105;   synthesis  of,  108 
Malt-sugar  (see  Maltose) 

Mammals,  appearance  of  lactase  in,  234,  235,  236 
M  \\<;anese  dioxide,  79 
Mass-action,  law  of,  84 
Mastication,  2;  muscles  concerned  in,  3;  nerves  concerned  in, 

3;  results  of  incomplete,  14 


342  INDEX  OF  SUBJECTS. 

Maxilla,  movements  of  lower,  3 

Meat,  and  gastric  secretion,  198,  211;  and  pancreatic  secretion, 
220 

Meat  broth  and  gastric  secretion,  211 

Meat  extract  and  gastric  secretion,  211,  231 

Meat  juice,  231 ;  and  gastric  secretion,  211 

Mechanical  affinity,  250;  of  colloids,  250 

Mechanical  stimulation  and  gastric  secretion,  232 

Membranes,  254;  permeability  of,  251;  classification  of,  254; 
semipermeable,  255;  permeable,  255;  precipitation,  255; 
of  copper  ferrocyanide,  255;  of  zinc  ferrocyanide,  255; 
animal,  255;  behavior  of  crystalloids  and  colloids  toward, 
256;  existence  of,  in  organism,  256,  266;  physiological,  257; 
cells  and  tissues  as,  257 

Micrococcus  restituens,  307 

Milk,  curdling  of,  67,  111;  mechanism  of  coagulation  of,  111; 
souring  of,  111;  effect  of  acids  on,  111;  and  caseinase,  111; 
theories  of  coagulation  of,  112 ;  relation  of  metals  to  curdling 
of,  113;  and  gastric  secretion,  198;  and  pancreatic  secre- 
tion, 217;  as  a  food,  232 

Milk-curdling  ferment  (see  Caseinase) 

Milk-sugar  (see  Lactose) 

Mind,  effect  of,  on  organs,  184 

Miniature  stomach,  189 

Molecular  solutions,  47  (see  also  Solutions) 

Monobutyrin,  analysis  and  synthesis  of,  by  lipase,  153 

Morphin,  elimination  of,  through  stomach,,  311 

Mouth,  mucous  glands  of,  185 

Movements,  of  mastication,  2 ;  of  deglutition,  3 ;  of  oesophagus, 
5 ;  of  stomach,  6 ;  of  small  intestine,  22 ;'  of  large  intestine, 
29;  of  food  through  alimentary  tract,  36 

Mucous  glands,  of  mouth,  64 ;  of  oesophagus,  65 

Mutton  tallow,  deposition  of,  after  feeding,  294 

Nervous  control  of  alimentary  tract,  41 
Nitrogen  tetroxide,  79 
Non-electrolytEj  260 

CEdema,  theory  of,  268 


INDEX  OF  SUBJECTS.  343 

(EsOPIIAGOTOMV,   I'M 

(Esophagi's,  mucous  glands  of,  65 

Olive-oil,  digestion  of,  239 

Optimum  temperature,  88 

Ornithin,  from  arginin,  158 

(  )smoTIC  cell,  202 

Osmotic  pressure,  258; of  non-electrolytes,  259;  of  electrolytes 

260;  and  semipermeable  membranes,  259;  laws  of,  259,  200; 

and    migration  of  water,   204;   behavior  of   cells    toward 

changes  in,  205,  206 
Oxidases,  82 

Pancreas,  amjdase  of,  91;  regulation  of  secretion  of,  215- 
fistuke  of,  215,  210;  normal  excitants  of,  224;  adaptation 
of  food  to,  234;  role  of,  in  fat  absorption,  290,  297,  298 ; 
importance  of,  in  protein  absorption,  302,  303,  304;  re- 
moval of,  303 

Pancreatic  duct,  occlusion  of,  303 

Pancreatic  juice,  08 ;  physical  properties  of,  09 ;  ferments  of, 
69;  human,  69,  70;  adaptation  of,  to  food,  234  (see  also 
Pancreas  and  Pancreatic  secretion) 

Pancreatic  secretin,  227 

Pancreatic  secretion,  effect  of  diet  on,  210;  quantitative 
variations  in,  217;  qualitative  variations  in,  217;  and  milk, 
217;  and  bread,  220;  and  meat,  220;  effect  of  vagus  on, 
222;  effect  of  sympathetic  on,  223;  inhibition  of,  222;  psy- 
chic excitation  of,  225;  normal  excitants  of,  224;  effects  of 
acids  on,  224;  effects  of  salts  on,  225;  effect  of  fat  on,  225; 
effect  of  water  on,  220;  significance  of  physiology  of,  230 

Paralytic  secretion,  of  saliva,  182;  of  small  intestine,  244 

Parotid  gland,  170,  177;  amount  of  secretion  from,  179 

Pepsin  (see  Acid-proteinasc) 

Peptides,  124;  synthesis  of,  141;  chemical  reactions  of,  142; 
digestion  of,  by  pancreatic  juice,  142 

Peptones,  124;,  analysis  of,  128,  147;  and  intestinal  mucosa, 
147;  and  gastric  secretion,  211;  effect  of,  on  blood  pres- 
sure, 304 

Permeability  of  gastro-intestinal  tract  in  one  direction,  279, 
280 


344  INDEX  OF  SUBJECTS. 

Permeable  membranes  (see  Membranes) 

Plasmolysis,  269 

Plastein,  143 

Platinum,  colloidal,  95 

Polariscope,  108 

Polypeptides,  125 

Polyuria,  314 

Precipitation  membranes  (see  Membranes) 

Proferments,  92;  of  alkali-proteinase,  92;  of  caseinase,  93; 
of  lipase,  93;  of  acid-proteinase,  93 

Protagon,  as  a  lipoid,  274 

Protease,  in  intestinal  juice,  75,  146;  isolation  of,  147;  diges- 
tion products  of,  148;  and  alkali-proteinase,  148;  and 
casein,  148 ;  substances  attacked  by,  148 ;  effect  of  medium 
on,  149 ;  and  proteolysis,  301 ;  physiological  importance  of, 
308,  309,  310 

Protein  digestion  (see  Proteolysis) 

Proteinases,  75  (see  also  Acid-,  Alkali-,  and  Ampho-proteinase) ; 
recognition  of,  129;  quantitative  estimation  of,  129;  rever- 
sible action  of,  140,  307,  308 

Proteins,  rate  of  leaving  stomach,  17;  digestion  of,  75,  300, 
301;  synthesis  of,  141,  146;  absorption  of,  299,  300;  chan- 
nels of  absorption  of,  302 ;  role  of  stomach  in  absorption  of, 
302,  303,  304;  role  of  pancreas  in  absorption  of,  302,  303, 
304;  role  of  intestine  in  absorption  of,  303;  fate  of  after 
digestion,  304,  305 ;  synthesis  of,  in  intestinal  wall,  306,  307 

Proteolysis,  products  of,  121,  125;  mechanism  of,  124;  dia- 
gram of,  127;   cleavage  theory  of,  128 

Proteolytic  ferments  (see  Proteinases) 

Proteoses,  124 

Pseudo-solutions  (see  Colloids  and  Colloidal  solutions) 

Psychic  secretion,  61;  of  gastric  juice,  203;  of  pancreatic 
juice,  225 

Ptyalin  (see  Amylase) 

Putrefaction  of  alimentary  contents,  242 

Pylorus,  behavior  of,  during  digestion,  12 ;  opening  and  closing 
of,  12,  14,  16;  rhythmic  opening  of,  230 

Radiographs,  7 


INDEX  OF  SUBJECTS.  345 

Reaction,  reversible,  107;  stationary,  107 
Reaction  velocity,  effect  of  temperature  on,  87 

RECTAIi  FEEMNG,  52 

Rennet  (see  Caseinase) 
Rennin  (see  Caseinase) 
Reversible  reaction,  107 
Reversion,  106 
Rubidium,  excretion  of,  313 

Saccharomyces,  157 
Saline  cathartics  (see  Cathartics) 

Saliva,  62,  176;  submaxillary,  63;  sublingual,  63;  mixed,  64; 
reaction  of,  64 ;  inorganic  constituents  of,  65 ;  organic  con- 
stituents of,  65;  ferments  of,  65;  chemical  composition  of, 
179;  secretion  of,  176,  182;  changes  in,  with  different  foods, 
183 ;  reflex  secretion  of,  185  (see  also  Salivary  glands  and 
Salivary  secretion) 
Salivary  calculi,  65 
Salivary  digestion,  in  stomach,  15 
Salivary  fistul/E,  temporary,  176;  permanent,  177 
Salivary  glands,  62 ;  parotid,  62 ;  exothermic  reactions  in,  182 ; 

psychology  of,  184;  elimination  of  iodides  through,  311 
Salivary  secretion,  regulation  of,  176,  177;  relation  of  nerves 
to,  178;  accessory  phenomena  of,  180,  181 ;  pressure  changes 
during,  181;  reflex,  182,  185;  and  mechanical  stimulation, 
183;   effect  of  alkaloids  on,  181;   effect  of  water  on,  183; 
effect  of  sand  on,  183;   effect  of  chemicals  on,  1S3;   effect 
of  foods  on,  183;  and  blood  pressure,  187 
Salts,   as  electrolytes,  260;  absorption  of,  274,  275,  276,  277, 
278,  279,  2S0,  281 ;  behavior  of  red  blood-corpuscles  toward, 
256;  alimentary  excretion  of,  312,  313 
Sea-sickness,  185 
Secretin,  pancreatic,  77,  227,  228;  gastric,  211;  as  excitant  of 

biliary  secretion,  238 
Secretion,  of  bile  (see  Biliary  secretion);  of  intestine  (see  In- 
testinal secretion);    pancreatic    (see  Pancreatic  secretion)] 
salivary  (see  Salivary  secretion) 
Segmentation,  movements  of,  in  intestine,  25,  26,  27  (see  also 
Intestine) 


346  INDEX  OF  SUBJECTS. 

Semipermeable  membranes,  255  (see  also  Membranes) 

Sham  feeding,  66,  191 

Sleep,  effect  of,  on  gastro-intestinal  movements,  46 

Small  intestine  (see  Intestine,  small) 

Soaps,  solubility  of,  242 

Sodium  bicarbonate,  and  gastric  secretion,  210 

Sodium  excretion,  313;  urinary  and  alimentary,  314 

Sodium  silicate,  absorption  of,  from  intestinal  tract,  256;  ab- 
sorption of  colloidal,  288,  289 

Sol,  95 

Solutions,  molecular,  47;  equimolecular,  47;  isotonic,  268; 
isosmotic,  268 ;  colloidal  or  pseudo  (see  Colloids  and  Col- 
loidal solutions);  crystalloidal,  251,  252,  253,  254 

Soup,  231 

Splanchnic  nerve,  effect  of,  on  gastric  movements,  42 

Spleen,  function  of,  during  digestion,  247 

Spores,  86 

Starch,  digestion  of,  76 ;  fermentation  of,  99 ;  effect  of  amylase 
on,  101;  effect  of  maltase  on,  104;  absorption  of,  285,  286 

Starvation  diabetes,  284,  285 

Stationary  reaction,  107 

Steapsin  (see  Lipase) 

Stomach,  movements  of,  6;  changes  in  shape  of,  during  diges- 
tion, 8,  9;  antrum  of,  8;  pylorus  of,  8;  preantral  part  of,  8 
muscle  layers  of,  9;   as  a  reservoir,  12;   emptying  of,  12 
time  food  spends  in,  13,  17;  movements  of  food  within,  14 
salivary  digestion  in,  15;   passage  of  food  out  of,  16,  17 
effect  of  vagus  nerve  on  movements  of,  42;  effect  of  sym- 
pathetic nerve  on  movements  of,  42 ;   effect  of  Auerbach 
and  Meissner's  plexus  on  movements  of,  43;  effect  of  emo- 
tional states  on  movements  of,  45;    post-mortem   diges- 
tion of,  136;    why  not  self -digested,  137;    ulcers  of,  138; 
bactericidal  action  of,   163;    anacidity  of,   165;    bacterial 
fermentation  in,  165;  importance  of,  in  protein  absorption 
302,  303;  removal  of,  302;  as  excretory  organ,  311;  char- 
acter of  contents  of,  318;  fistulae  of,  188;  miniature,  189 

Strontium,  alimentary  excretion  of,  312 

Sublingual  gland,  176,  177 

Submaxillary  gland,  176,  177;  amount  of  secretion  from,  179 


INDEX  OF  SUBJECTS.  347 

SuCCUS  ENTERICUS    (sec  Intestinal  juice  ;nul  Intestinal  Secretion) 

Sucklings,  lactase  in,  235 

Sucrase,  of  intestine,  70,  L53;   distribution  of,  154;   isolation 

of,  154;  effecl  of  external  conditions  on,  155 
Sucrose,  digestion  of,  76,  153;   inversion  of,  by  sucrase,  155; 

inversion  of,  by  acids,  155; 
Sugars,  absorption  of,  2S5;  excretion  of,  into  intestine,  315,  31G 
Sulphocyanate,  of  saliva,  63 
Sulphuric  acid,  manufacture  of,  79,  83 
Swallowing  (see  Deglutition) 
Sympathetic  nerve,  effect  of,  in  gastric  movements,  42;  effect 

of,  on  pancreas,  223;   and  salivary  secretion,  178 
Synaptase,  velocity  of  decomposition  of,  88 

Tartar,  65 

Toxins,  139 

Triacetin,  pancreatic  digestion  of,  240,  241 

Trifacial  nerve,  and  salivary  glands,  178 

Triolein,  analysis  and  synthesis  of,  153 

Trypsin  (see  Alkali-proteinase) 

Typical  colloids,  252  (see  also  Colloids) 

Ulcers  of  alimentary  tract,  138 

Units,  ferment,  220 

Urea,  from  arginin,  158;  in  alimentary  secretions,  315 

Vagotomy,  201 

Vagus,  effect  of,  on  gastric  movements,  42;  effect  of,  on  intes- 
tinal movements,  43;  and  gastric  secretion,  222;  and 
pancreatic  secretion,  222 

VlSCOSIMETER,   131 

Viscosity,  determination  of,  131;  of  proteins,  131,  144 
Vital  properties,  SI 

Water,  with  meals,  104;  as  excitant  of  gastric  secretion,  226, 
232;  as  excitant  of  pancreatic  secretion,  22(1;  absorption  of, 
262,  269 ;  absorption  of,  by  colloids,  250;  osmotic  absorption 
of,  264  (see  also  Ahsur/ilion) 


348  INDEX  OF  SUBJECTS. 

Whey,  112 

Worms,  why  intestinal,  are  not  digested,  135 

X-ray  in  study  of  intestinal  movements,  7 

Zymogens,  92,  93 


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4 


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Winton's  Microscopy  of  Vegetable  Foods 8vo,  7  50 

Wulling's    Elementary    Course    in  Inor^auic,  Pharmaceutical,  and  Medical 

Chemistry i2mo,  2  00 


CIVIL  ENGINEERING. 

BRIDGES    AND    ROOFS.       HYDRAULICS.       MATERIALS    OF    ENGINEERING. 
RAILWAY  ENGINEERING. 

Baker's  Engineers'  Surveying  Instruments i2mo,  3  00 

Bixby's  Graphical  Computing  Table Paper  19^X24^  inches.  25 

Breed  and  Hosmer's  Principles  and  Practice  of  Surveying 8vo,  3  00 

*  Burr's  Ancient  and  Modern  Engineering  and  the  Isthmian  Canal .  8vo,  3  50 

Comstock's  Field  Astronomy  for  Engineers 8vo,  2  50 

Crandall's  Text-book  on  Geodesy  and  Least  Squares 8vo,  3  00 

Davis's  Elevation  and  Stadia  Tables 8vo,  1  00 

Elliott's  Engineering  for  Land  Drainage nmo,  1  50 

Practical  Farm  Drainage i2mo,  1  00 

*Fiebeger's  Treatise  on  Civil  Engineering 8vo,  5  00 

Flemer's  Phototopographic  Methods  and  Instruments • 8vo,  5  00 

Folwell's  Sewerage.     (Designing  and  Maintenance.) 8vo,  3  00 

Freitag's  Architectural  Engineering.     2d  Edition,  Rewritten 8vo,  3  50 

French  and  Ives's  Stereotomy 8vo,  2  50 

Goodhue's  Municipal  Improvements i2mo,  1  75 

Gore's  Elements  of  Geodesy 8vo,  2  50 

Hayford's  Text-book  of  Geodetic  Astronomy 8vo,  3  00 

Hering's  Ready  Reference  Tables  (Conversion  Factors') i6mo,  morocco,  2  50 

Howe's  Retaining  Walls  for  Earth nmo,  1   25 

*  Ives's  Adjustments  of  the  Engineer's  Transit  and  Level i6mo,  Bds.  25 

Ives  and  Hilts's  Problems  in  Surveying i6mo,  morocco,  1  50 

Johnson's  (J.  B.)  Theory  and  Practice  of  Surveying Small  8vo,  4  00 

Johnson's  (L.  J.)  Statics  by  Algebraic  and  Graphic  Methods 8vo,  2  00 

Laplace's  Philosophical  Essay  on  Probabilities.     (Truscott  and  Emory.) .  nmo,  2  00 

Mahan's  Treatise  on  Civil  Engineering.     (1873.)     (Wood.) 8vo,  5  00 

*  Descriptive  Geometry 8vo, 

Merriman's  Elements  of  Precise  Surveying  and  Geodesy 8vo, 

Merriman  and  Brooks's  Handbook  for  Surveyors i6mo,  morocco, 

Nugent's  Plane  Surveying 8vo, 

Ogden's  Sewer  Design i2mo, 

Parsons's  Disposal  of  Municipal  Refuse 8vo, 

Patton's  Treatise  on  Civil  Engineering 8vo  half  leather, 

Reed's  Topographical  Drawing  and  Sketching 4to, 

Rideal's  Sewage  and  the  Bacterial  Purification  of  Sewage 8vo, 

Siebert  and  Biggin's  Modern  Stone-cutting  and  Masonry 8vo, 

6 


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2 

50 

2 

00 

3 

50 

2 

00 

2 

00 

7 

50 

5 

00 

4 

00 

Smith'.;  Manual  ui  Topographical  Drawing.      (McMillan.; 8vo,  2  50 

Sondericker's  Graphic  Statics,  with  Applications  to  1  russes.  Beams,  and  Arches. 

8vo,  2  00 

Taylor  and  Thompson's  Treatise  on  Concrete,  Plain  and  Reinfoiced 8vo,  5  00 

*  Trautwir.e's  Civil  Engineer's  Pocket-book i6mo,  morocco,  5  00 

Venable's  Garbage  Crematories  in  America 8vo,  2  00 

Wait's  Engineering  and  Architectural  Jurisprudence 8vo  6  00 

Sheep,  6  50 
Law  of  Operations  Preliminary  to  Construction  in  Engineering  and  Archi- 
tecture  8vo,  s  00 

Sheep,  5  50 

Law  of  Contracts 8vo,  3  00 

Warren's  Stereotomy — Problems  in  Stone-cutting 8vo,  2  50 

Webb's  Problems  in  the  Use  and  Adjustment  of  Engineering  Instruments. 

i6mo,  morocco,  1  25 

Wilson's  Topographic  Surveying 8vo,  3  50 


BRIDGES  AND   ROOFS. 

Boiler's  Practical  Treatise  on  the  Construction  of  Iron  Highway  Bridges.  .  8vo,  2  00 

*       Thames  River  Bridge 4to,  paper,  5  00 

Burr's  Course  on  the  Stresses  in  Bridges  and  Roof  Trusses,  Arched  Rihs,  and 

Suspension  Bridges 8vo,  3  50 

Burr  and  Falk's  Influence  Lines  for  Bridge  and  Roof  Computations 8vo,  3  00 

Design  and  Construction  of  Metallic  Bridges 8vo  5  00 

Du  Bois's  Mechanics  of  Engineering.     Vol.  II Small  4to,  10  co 

Foster's  Treatise  on  Wooden  Trestle  Bridges 4to,  5  00 

Fowler's  Ordinary  Foundations 8vo,  3  50 

Greene's  Roof  Trusses 8vo,  1  25 

Bridge  Trusses 8vo,  2  50 

Arches  in  Wood,  Iron,  and  Stone 8vo  2  50 

Howe's  Treatise  on  Arches 8vo,  4  00 

Design  of  Simple  Roof-trusses  in  Wood  and  Steel » 8vo,  2  00 

Symmetrical  Masonry  Arches 8vo,  2  50 

Johnson,  Bryan,  and  Turneaure's  Theory  and  Practice  in  the  Designing  of 

Modern  Framed  Structures Small  4to,  10  00 

Merriman  and  Jacoby's  Text-book  on  Roofs  and  Bridges: 

Part  I.     Stresses  in  Simple  Trusses 8vo,  2  50 

Part  II.    Graphic  Statics 8vo,  2  50 

Part  III.   Bridge  Design 8vo,  2  50 

Part  IV.    Higher  Structures 8vo,  2  50 

Morison's  Memphis  Bridge 4to,  10  00 

Waddell's  De  Pontibus,  a  Pocket-book  for  Bridge  Engineers.  .  i6mo,  morocco,  2  00 

*  Specifications  for  Steel  Bridges nmo,  50 

Wright's  Designing  of  Draw-spans.     Two  parts  in  one  volume 8vo,  3  50 


HYDRAULICS. 

Barnes's  Ice  Formation 8vo,  3  00 

Bazin's  Experiments  upon  the  Contraction  of  the  Liquid  Vein  Issuing  from 

an  Orifice.     (Trautwine.) 8vo,  2  00 

Bovey's  Treatise  on  Hydraulics 8vof  5  00 

Church's  Mechanics  of  Engineering 8vo,  6  00 

Diagrams  of  Mean  Velocity  of  Water  in  Open  Channels paper,  1  50 

Hydraulic  Motors 8vo,  2   00 

Coffin's  Graphical  Solution  of  Hydrr.ulic  Problems i6mo,  morocco,  2  50 

Flather's  Dynamometers,  and  the  Measurement  of  Power i2mo,  3  00 

7 


Folwell's  Water-supply  Engineering 8vo,  4  00 

Frizell's  Water-power 8vo,  5  00 

Fuertes's  Water  and  Public  Health nmo,  1  50 

Water-filtration  Works i2mo,  2  50 

Ganguillet  and  Kutter's  General  Formula  for  the  Uniform  Flow  of  Water  in 

Rivers  and  Other  Channels.     (Hering  and  Trautwine.) 8vo,  4  00 

Hazen's  Filtration  of  Public  Water-supply 8vo,  3  00 

Hazlehurst's  Towers  and  Tanks  for  Water- works 8vo,  2  50 

Herschel's  115  Experiments  on  the  Carrying  Capacity  of  Large,  Riveted,  Metal 

Conduits 8vo,  2  00 

Mason's  Water-supply.     (Considered  Principally  from  a  Sanitary  Standpoint.) 

8vo,  4  00 

Merriman's  Treatise  on  Hydraulics 8vo,  5  00 

*  Michie's  Elements  of  Analytical  Mechanics 8vo,  4  00 

Schuyler's   Reservoirs   for   Irrigation,   Water-power,   and   Domestic   Water- 
supply Large  8vo,  5  00 

*  Thomas  and  Watt's  Improvement  of  Rivers 4to,  6  00 

Turneaure  and  Russell's  Public  Water-supplies 8vo,  5  00 

Wegmann's  Design  and  Construction  of  Dams 4to,  5  00 

Water-supply  of  the  City  of  New  York  from  1658  to  1895 4to,  10  00 

Whipple's  Value  of  Pure  Water Large  nmo,  1   00 

Williams  and  Hazen's  Hydraulic  Tables 8vo,  1  50 

Wilson's  Irrigation  Engineering Small  8vo,  4  00 

Wolff's  Windmill  as  a  Prime  Mover 8vo,  3  00 

Wood's  Turbines 8vo,  2  50 

Elements  of  Analytical  Mechanics 8vo,  3  00 


MATERIALS  OF  ENGINEERING. 

Baker's  Treatise  on  Masonry  Construction 8vo, 

Roads  and  Pavements 8vo, 

Black's  United  States  Public  Works Oblong  4to, 

*  Bovey's  Strength  of  Materials  and  Theory  of  Structures 8vo, 

Burr's  Elasticity  and  Resistance  of  the  Materials  of  Engineering 8vo, 

Byrne's  Highway  Construction 8vo, 

Inspection  of  the  Materials  and  Workmanship  Employed  in  Construction. 

i6mo, 

Church's  Mechanics  of  Engineering 8vo, 

Du  Bois's  Mechanics-of  Engineering.     Vol.  I. Small  4to, 

*Eckel's  Cements,  Limes,  and  Plasters 8vo, 

Johnson's  Materials  of  Construction Large  8vo, 

Fowler's  Ordinary  Foundations 8vo, 

Graves's  Forest  Mensuration 8vo, 

*  Greene's  Structural  Mechanics 8vo, 

Keep's  Cast  Iron 8vo, 

Lanza's  Applied  Mechanics 8vo, 

Marten's  Handbook  on  Testing  Materials.     (Henning.)     2  vols 8vo, 

Maurer's  Technical  Mechanics 8vo, 

Merrill's  Stones  for  Building  and  Decoration 8vo, 

Merriman's  Mechanics  of  Materials 8vo, 

*  Strength  of  Materials i2mo, 

Metcalf's  Steel.     A  Manual  for  Steel-users i2mo, 

Patton's  Practical  Treatise  on  Foundations 8vo, 

Richardson's  Modern  Asphalt  Pavements 8vo, 

Richey's  Handbook  for  Superintendents  of  Construction i6mo,  mor.,    4  00 

*  Ries's  Clays:  Their  Occurrence,  Properties,  and  Uses 8vo,    5  00 

Rockwell's  Roads  and  Pavements  in  France i2mo,    1  25 


5 

00 

5 

00 

5 

00 

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7 

50 

5 

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3 

00 

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7 

50 

6 

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6 

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00 

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50 

2 

50 

7 

50 

7 

50 

4 

00 

5 

00 

S 

00 

1 

00 

2 

00 

5 

00 

3 

00 

Sabin's  Industrial  and  Artistic  Technology  of  Paints  ard  Varnish 8vo,  3  00 

Smith's  Materials  of  Machines. i2mo,  1  00 

Snow's  Principal  Species  of  Wood 8vo,  3  50 

Spalding's  Hydraulic  Cement nnw,  2  00 

Text-book  on  Roads  and  Pavements i2mo,  2  00 

Taylor  and  Thompson's  Treatise  on  Concrete,  Plain  and  Reinforced 8vo,  5  00 

Thurston's  Materials  of  Engineering.      3  Parts 8vo,  8  00 

Part  I.     Non-metallic  Materials  of  Engineering  and  Metallurgy 8vo,  2  00 

Part  II.     Iron  and  Steel 8vo,  3  50 

Part  III.     A  Treatise  on  Brasses,  Bronzes,  and  Other  Alloys  and  their 

Constituents 8vo,  2  50 

Tillson's  Street  Pavements  and  Paving  Materials 8vo,  4  00 

Waddell's  De  Pontibus.    (A  Pocket-book  for  Bridge  Engineers.) ..  i6mo,  mor.,  2  00 

*         Specifications  for  Steel  Bridges i2mo,  50 

Wood's  (De  V.)  Treatise  on  the  Resistance  of  Materials,  and  an  Appendix  on 

the  Preservation  of  Timber 8vo,  2  00 

Wood's  (De  V.)  Elements  of  Analytical  Mechanics 8vo,  3  00 

Wood's  (M.  P.)  Rustless  Coatings:    Corrosion  and  Electrolysis  of  Iron  and 

Steel 8vo,  4  00 


RAILWAY   ENGINEERING. 

Andrew's  Handbook  for  Street  Railway  Engineers 3x5  inches,  morocco,     1  25 

Berg's  Buildings  and  Structures  of  American  Railroads 4to,     5  00 

Brook's  Handbook  of  Street  Railroad  Location i6mo,  morocco, 

Butt's  Civil  Engineer's  Field-book i6mo,  morocco, 

Crandall's  Transition  Curve i6mo,  morocco, 

Railway  and  Other  Earthwork  Tables 8vo, 

Dawson's  "Engineering"  and  Electric  Traction  Pocket-book.  .  i6mo,  morocco, 

Dredge's  History  of  the  Pennsylvania  Railroad:    (1879) Paper, 

Fisher's  Table  of  Cubic  Yards Cardboard, 

Godwin's  Railroad  Engineers'  Field-book  and  Explorers'  Guide.  .  .  i6mo,  mor., 
Hudson's  Tables  for  Calculating  the  Cubic  Contents  of  Excavations  and  Em- 
bankments  8vo,     1  00 

Molitor  and  Beard's  Manual  for  Resident  Engineers i6mo,     1   00 

Nagle's  Field  Manual  for  Railroad  Engineers i6mo,  morocco,     3  00 

Philbrick's  Field  Manual  for  Engineers i6mo,  morocco,     3  00 

Searles's  Field  Engineering i6mo,  morocco,    3  00 

Railroad  Spiral i6mo,  morocco,     1  50 

Taylor's  Prismoidal  Formulae  and  Earthwork 8vo,     1   50 

*  Trautwine's  Method  of  Calculating  the  Cube  Contents  of  Excavations  and 

Embankments  by  the  Aid  of  Diagrams 8vo,     2  00 

The  Field  Practice  of  Laying  Out  Circular  Curves  for  Railroads. 

i2mo,  morocco,    2  50 

Cross-section  Sheet Paper,         25 

Webb's  Railroad  Construction i6mo,  morocco,     5  00 

Economics  of  Railroad  Construction Large  i2mo,     2   50 

Wellington's  Economic  Theory  of  the  Location  of  Railways Small  8vo,    5  00 


DRAWING. 

Barr's  Kinematics  of  Machinery 8vo,  2  50 

*  Bartlett's  Mechanical  Drawing 8vo,  3  00 

*  "  "  "         Abridged  Ed 8vo,  1  5° 

Coolidge's  Manual  of  Drawing 8vo,  paper,  1  00 

9 


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2 

50 

I 

50 

I 

50 

5 

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5 

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as 

2 

50 

2 

50 

2 

00 

I 

50 

3 

00 

3 

00 

5 

oo 

4 

oo 

I 

50 

i 

SO 

i 

50 

3 

50 

Coolidge  and  Freeman's  Elements  of  General  Drafting  for  Mechanical  Engi- 
neers  Oblong  4to, 

Durley's  Kinematics  of  Machines 8vo, 

Emch's  Introduction  to  Projective  Geometry  and  its  Applications 8vo, 

Hill's  Text-book  on  Shades  and  Shadows,  and  Perspective. 8vo, 

Jamison's  Elements  of  Mechanical  Drawing 8vo, 

Advanced  Mechanical  Drawing 8vo, 

Jones's  Machine  Design: 

Part  I.     Kinematics  of  Machinery 8vo, 

Part  II.     Form,  Strength,  and  Proportions  of  Parts 8vo, 

MacCord's  Elements  of  Descriptive  Geometry 8vo, 

Kinematics ;   or,  Practical  Mechanism 8vo, 

Mechanical  Drawing 4to, 

Velocity  Diagrams 8vo, 

MacLeod's  Descriptive  Geometry Small  8vo, 

*  Mahan's  Descriptive  Geometry  and  Stone-cutting 8vo, 

Industrial  Drawing.     (Thompson.) 8vo, 

Moyer's  Descriptive  Geometry 8vo,    2  00 

Reed's  Topographical  Drawing  and  Sketching 4to,    5  00 

Reid's  Course  in  Mechanical  Drawing 8vo,    2  00 

Text-book  of  Mechanical  Drawing  and  Elementary  Machine  Design. 8vo,    3  00 

Robinson's  Principles  of  Mechanism ;  .  .  .  8vo,    3  00 

Schwamb  and  Merrill's  Elements  of  Mechanism 8vo,    3  00 

Smith's  (R.  S.)  Manual  of  Topographical  Drawing.     (McMillan.) 8vo,    2  50 

Smith  (A.  W.)  and  Marx's  Machine  Design 8vo,    3  00 

*  Titsworth's  Elements  of  Mechanical  Drawing Oblong  8vo,     1  25 

Warren's  Elements  of  Plane  and  Solid  Free-hand  Geometrical  Drawing.  i2mo,     1  00 

Drafting  Instruments  and  Operations i2mo,     1  25 

Manual  of  Elementary  Projection  Drawing i2mo,     1  50 

Manual  of  Elementary  Problems  in  the  Linear  Perspective  of  Form  and 

Shadow i2mo,     1  00 

Plane  Problems  in  Elementary  Geometry i2mo,     1  25 

Primary  Geometry. i2mo,         75 

Elements  of  Descriptive  Geometry,  Shadows,  and  Perspective 8vo,    3  50 

General  Problems  of  Shades  and  Shadows 8vo,    3  00 

Elements  of  Machine  Construction  and  Drawing 8vo,     7  50 

Problems,  Theorems,  and  Examples  in  Descriptive  Geometry 8vo,    2  50 

Weisbach's    Kinematics    and    Power    of    Transmission.        (Hermann    and 

Klein.) 8vo,    5  00 

Whelpley's  Practical  Instruction  in  the  Art  of  Letter  Engraving nmo,     2  00 

Wilson's  (H.  M.)  Topographic  Surveying 8vo,    3  50 

Wilson's  (V.  T.)  Free-hand  Perspective 8vo.     2  50 

Wilson's  (V.  T.)  Free-hand  Lettering 8vo,     1  00 

Woolf's  Elementary  Course  in  Descriptive  Geometry Large  8vo,    3  00 


ELECTRICITY  AND   PHYSICS. 

*  Abegg's  Theory  of  Electrolytic  Dissociation.     (Von  Ende.) i2mo,  1  25 

Anthony  and  Brackett's  Text-book  of  Physics.     (Magie.) Small  8vo  3  00 

Anthony's  Lecture-notes  on  the  Theory  of  Electrical  Measurements.  .  .  .  i2mo,  1  00 

Benjamin's  History  of  Electricity 8vo,  3  00 

Voltaic  Cell 8vo,  3  00 

Classen's  Quantitative  Chemical  Analysis  by  Electrolysis.     (Boltwood.).8vo,  3  00 

*  Collins's  Manual  of  Wireless  Telegraphy i2mo,  1  50 

Morocco,  2  00 

Crehore  and  Squier's  Polarizing  Photo-chronograph 8vo,  3  00 

*  Danneel's  Electrochemistry.     (Merriam.) i2mo,  1  25 

Dawson's  "Engineering"  and  Electric  Traction  Pocket-book.  i6mo,  morocco,  5  00 

10 


Dolezalek's    Theory    of    the    Lead    Accumulator    ( Storage    Battery).       'Von 

Ende.) i2mo,  2  50 

Duhem's  Thermodynamics  and  Chemistry.     (Burgess.) 8vo,  4  00 

Flather's  Dynamometers,  and  the  Measurement  of  Power i2mo,  3  00 

Gilbert's  De  Magnete.     (Mottelay. ) 8vo,  2  50 

Hanchett's  Alternating  Currents  Explained i2mo,  1  00 

Hering's  Ready  Reference  Tables  (Conversion  Factors) i6mo   morocco,  2  50 

Holman's  Precision  of  Measurements 8vo,  2  00 

Telescopic    Mirror-scale  Method,  Adjustments^  and   Tests.  ..  .Large  8vo,  75 

Kinzbrunner's  Testing  of  Continuous-current  Machines 8vo,  2  00 

Landauer's  Spectrum  Analysis.     (Tingle.) 8vo,  3  00 

Le  Chatelier  s  High-temperature  Measurements.  (Boudouard — Burgess.)  i2mo,  3  00 

Lc'ib's  Electrochemistry  of  Organic  Compounds.     (Lorenz. ) 8vo,  3  00 

*  Lyons'?  Treatise  on  Electromagnetic  Phenomena.   Vols.  I.  and  II.  8vo,  each,  6  00 

*  Michie's  Elements  of  Wave  Motion  Relating  to  Sound  and  Light 8vo,  4  00 

Niaudet's  Elementary  Treatise  on  Electric  Batteries.     (Fishback.) i2mo,  2  50 

*  Parshall  and  Hobart's  Electric  Machine  Design 4to,  half  morocco,  12  50 

Reagan's  Locomotives:    Simple,  Compound,  and  Electric.      New  Edition. 

Large  nmo,  3  50 

*  Rosenberg's  Electrical  Engineering.     (Haldane  Gee — Kinzbrunner.).  .  .8vo,  2  00 

Ryan,  Norris,  and  Hoxie's  Electrical  Machinery.     Vol.  1 8vo,  2  50 

Thurston's  Stationary  Steam-engines 8vo,  2  5« 

*  Tillman's  Elementary  Lessons  in  Heat 8vo,  1  50 

Tory  and  Pitcher's  Manual  of  Laboratory  Physics Small  8vo,  2  00 

Ulke's  Modern  Electrolytic  Copper  Refining 8vo,  3  00 


LAW. 

*  Davis's  Elements  of  Law 8vo, 

*  Treatise  on  the  Military  Law  of  United  States 8vo, 

*  Sheep, 

*  Dudley's  Military  Law  and  the  Procedure  of  Courts-martial  .  .    .Large  nmo, 

Manual  for  Courts-martial. i6mo,  morocco, 

Wait's  Engineering  and  Architectural  Jurisprudence 8vo, 

Sheep, 
Law  of  Operations  Preliminary  to  Construction  in  Engineering  and  Archi- 
tecture  8vo 

Sheep, 

Law  of  Contracts 8vo, 

Winthrop's  Abridgment  of  Military  Law i2mo, 


MANUFACTURES. 

Bernadou'S  Smokeless  Powder — Nitro-cellulose  and  Theory  of  tte  Cellulose 

Molecule i2mo, 

Bolland's  Iron  Founder nmo, 

The  Iron  Founder,"  Supplement 1 2mo, 

Encyclopedia  of  Founding  and  Dictionary  of  Foundry  Terms  Used  in  the 
Practice  of  Moulding i2mo, 

*  Claassen's  Beet-sugar  Manufacture.    (Hall  and  Rolfe.) 8vo, 

*  Eckel's  Cements,  Limes,  and  Plasters , 8vo, 

Eissler's  Modern  High  Explosives 8vo, 

Effront's  Enzymes  and  their  Applications.     (Prescott.) 8vo, 

Fitzgerald's  Boston  Machinist i2mo, 

Ford's  Boiler  Making  for  Boiler  Makers i8mo, 

Hopkin's  Oil-chemists'  Handbook 8vo, 

Keep's  Cast  Iron 8vo, 

11 


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2 

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00 

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50 

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Leach's  The  Inspection  and  Analysis  of  Food  with  Special  Reference  to  State 

Control. Large  8vo,    7  50 

*  McKay  and  Larsen's  Principles  and  Practice  of  Butter-making 8vo,     1  50 

Matthews's  The  Textile  Fibres 8vo,    3  50 

Metcalf's  Steel.     A  Manual  for  Steel-users: nmo,    2  00 

Metcalfe'f  Cost  of  Manufactures — And  the  Administration  of  Workshops. 8vo,    5  00 

Meyer's  Modern  Locomotive  Construction 4to,  10  00 

Morse's  Calculations  used  in  Cane-sugar  Factories i6mo,  morocco,     1  50 

*  Reisig's  Guide  to  Piece-dyeing 8vo,  25  00 

Rice's  Concrete-block  Manufacture 8vo,    2  00 

Sabin's  Industrial  and  Artistic  Technology  of  Paints  and  Varnish 8vo, 

Smith's  Press-working  of  Metals 8vo, 

Spalding's  Hydraulic  Cement i2mo, 

Spencer's  Handbook  for  Chemists  of  Beet-sugar  Houses.  ....  i6mo  morocco, 

Handbook  for  Cane  Sugar  Manufacturers i6mo  morocco, 

Taylor  and  Thompson's  Treatise  on  Concrete,  Plain  and  Reinforced 8vo, 

Thurston's  Manual  of  Steam-boilers,  their  Designs,  Construction  and  Opera- 
tion  8vo, 

*  Walke's  Lectures  on  Explosives 8vo, 

Ware's  Beet-sugar  Manufacture  and  Refining Small  8vo, 

Weaver's  Military  Explosives 8vo, 

West's  American  Foundry  Practice i2mo, 

Moulder's  Text-book i2mo, 

Wolff's  Windmill  as  a  Prime  Mover 8vo, 

Wood's  Rustless  Coatings:   Corrosion  and  Electrolysis  of  Iron  and  Steel.  .8vo, 


MATHEMATICS. 

Baker's  Elliptic  Functions.  t. 8vo,  1  50 

*  Bass's  Elements  of  Differential  Calculus. i2mo,  4  00 

Briggs's  Elements  of  Plane  Analytic  Geometry i2mo,  1  00 

Compton's  Manual  of  Logarithmic  Computations i2mo  1  50 

Davis's  Introduction  to  the  Logic  of  Algebra 8vo,  1  50 

*  Dickson's  College  Algebra Large  i2mo,  1  50 

*  Introduction  to  the  Theory  of  Algebraic  Equations. Large  i2mo,  1  25 

Emch's  Introduction  to  Projective  Geometry  and  its  Applications 8vo  2  50 

Halsted's  Elements  of  Geometry 8vo,  1   75 

Elementary  Synthetic  Geometry. 8vo,  1  50 

Rational  Geometry i2mo,  1  75 

*  Johnson's  (J.  B.)  Three-place  Logarithmic  Tables:   Vest-pocket  size. paper,  15 

100  copies  for  5  00 

*  Mounted  on  heavy  cardboard,  8X 10  inches,  25 

10  copies  for  2  00 

Johnson's  (W.  W.)  Elementary  Treatise  on  Differential  Calculus .  .  Small  8vo,  3  00 

Elementary  Treatise  on  the  Integral  Calculus SmalI*8vo,  1  50 

Johnson's  (W.  W.)  Curve  Tracing  in  Cartesian  Co-ordinates. i2mo,  1  00 

Johnson's  (W.  W.)  Treatise  on  Ordinary  and  Partiar  Differential  Equations. 

Small  8vo,  3  50 

Johnson's  (W,  W.)  Theory  of  Errors  and  the  Method  of  Least  Squares,  nmo,  1  50 

*  Johnson's  (W   W.)  Theoretical  Mechanics i2mo,  3  00 

Laplace's  Philosophical  Essay  on  Probabilities.    (Truscott  and  Emory.).  i2mo,  2  00 

*  Ludlow  and  Bass.     Elements  of  Trigonometry  and  Logarithmic  and  Other 

Tables 8vo,  3  00 

Trigonometry  and  Tables  published  separately Each,  2  oc 

*  Ludlow's  Logarithmic  and  Trigonometric  Tables. 8vo  1  00 

Manning's  Irrational  Numbers  and  their  Representation  by  Sequences  and  Series 

i2mo,  1  25 

12 


Mathematical  Monographs.      Edited  by  Mansfield  Merriman  and  Robert 

S.  Woodward. Octavo,  each     I  oo 

No.  i.  History  of  Modern  Mathematics,  by  David  Eugene  Smith. 
No.  2.  Synthetic  Projective  Geometry,  by  George  Bruce  Halsted. 
No.  3.  Determinants,  by  Laenas  Gifford  Weld.  No.  4.  Hyper- 
bolic Functions,  by  James  McMahon.  No.  5.  Harmonic  Func- 
tions, by  William  E.  Byerly.  No.  6.  Grassmann's  Space  Analysis, 
by  Edward  W.  Hyde.  No.  7.  Probability  and  Theory  of  Errors, 
by  Robert  S.  Woodward.  No.  8.  Vector  Analysis  and  Quaternions, 
by  Alexander  Macfarlane.  No.  q.  Differential  Equations,  by 
William  Woolsey  Johnson.  No.  10.  The  Solution  of  Equations, 
by  Mansfield  Merriman.  No.  n.  Functions  of  a  Complex  Variable, 
by  Thomas  S.  Fiske. 

Maurer's  Technical  Mechanics 8vo,    4  00 

Merriman's  Method  of  Least  Squares 8vo,    2  00 

Rice  and  Johnson's  Elementary  Treatise  on  the  Differential  Calculus. .  Sm.  8vo,    3  00 

Differential  and  Integral  Calculus.     2  vols,  in  one Small  8vo,    2  50 

*  Veblen  and  Lennes's  Introduction  to  the  Real  Infinitesimal  Analysis  of  One 

Variable 8vo,    2  00 

Wood's  Elements  of  Co-ordinate  Geometry 8vo,    2  00 

Trigonometry:   Analytical,  Plane,  and  Spherical i2mo,     1  00 


MECHANICAL   ENGINEERING. 

MATERIALS  OF  ENGINEERING,  STEAM-ENGINES  AND  BOILERS. 

Bacon's  Forge  Practice i2mo,  1  50 

Baldwin's  Steam  Heating  for  Buildings i2mo,  2  50 

Barr's  Kinematics  of  Machinery 8vo,  2  50 

*  Bartlett's  Mechanical  Drawing 8vo,  3  00 

*  "  "        Abridged  Ed 8vo,     1  50 

Benjamin's  Wrinkles  and  Recipes nmo,    2  00 

Carpenter's  Experimental  Engineering 8vo, 

Heating  and  Ventilating  Buildings 8vo, 

Clerk's  Gas  and  Oil  Engine Small  8vo, 

Coolidge's  Manual  of  Drawing 8vo,  paper, 

Coolidge  and  Freeman's  Elements  of  General  Drafting  for  Mechanical  En- 
gineers  Oblong  4to, 

Cromwell's  Treatise  on  Toothed  Gearing i2mo, 

Treatise  on  Belts  and  Pulleys i2mo, 

Durley's  kinematics  of  Machines 8vo, 

Flather's  Dynamometers  and  the  Measurement  of  Power 1  21110, 

Rope  Driving nmo, 

Gill's  Gas  and  Fuel  Analysis  for  Engineers nmo, 

Hall's  Car  Lubrication i2mo, 

Herintr's  Ready  Reference  Tables  (Conversion  Factors') i6mo,  morocco, 

Hutton's  The  Gas  Engine 8vo, 

Jamison's  Mechanical  Drawing 8vo, 

Jones's  Machine  Design: 

Part  I.     Kinematics  of  Machinery 8vo, 

Part  II.     Form,  Strength,  and  Proportions  of  Parts 8vo, 

Kent's  Mechanical  Engineers'  Pocket-book i6mo,  morocco, 

Kerr's  Power  and  Power  Transmission 8vo, 

Leonard's  Machine  Shop,  Tools,  and  Methods 8vo, 

*  Lorenz's  Modern  Refrigerating  Machinery.    ( Pope,  Haven,  and  Dean.)  .  .  8vo, 
MacCord's  Kinematics;   cr.  Practical  Mechanism 8vo, 

Mechanical  Drawing 4to, 

Velocity  Diagrams 8vo, 

13 


6 

00 

4 

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4 

00 

I 

00 

2 

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I 

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I 

50 

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no 

2 

50 

5 

00 

2 

50 

1 

50 

3 

on 

5 

OO 

2 

00 

4 

o^> 

4 

on 

5 

00 

4 

no 

MacFarland's  Standard  Reduction  Factors  for  Gases 8vo,  i  50 

Hahan's  Industrial  Drawing.     (Thompson.) 8vo  3  50 

Pooies  Calorific  Power  of  Fuels 8vo,  3  00 

Reid's  Course  in  Mechanical  Drawing 8vo,  2  00 

Text-book  of  Mechanical  Drawing  and  Elementary  Machine  Design. 8vo,  3  00 

Richard's  Compressed  Air i2mo,  1   50 

Robinson's  Principles  of  Mechanism 8vo,  3  00 

Scb.war.ib  and  Merrill's  Elements  of  Mechanism 8vo,  3  00 

Smith's  (O.)  Press-working  of  Metals 8vo  3  co 

Smith  (A.  W.)  and  Marx's  Machine  Design 8vo,  3  00 

Thurston's   Treatise    on   Friction  and   Lost   Work   in   Machinery   and   Mill 

Work 8vo»  3  00 

Animal  as  a  Machine  and  Prime  Motor,  and  the  Laws  of  Energetics.  i2mo,  1  00 

Tillson's  Complete  Automobile  Instructor i6mo,  1  50 

Morocco,  2  00 

Warren's  Elements  of  Machine  Construction  and  Drawing 8vo,  7  50 

Weisbacb's    Kinematics    and    the    Power    of    Transmission.     (Herrmann — 

Klein.) 8vo,  5  00 

Machinery  of  Transmission  and  Governors.     (Herrmann — Klein.).  .8vo,  5  00 

Wolff's  Windmill  as  a  Prime  Mover 8vo,  3  00 

Wood's  Turbines 8vo,  2  50 


MATERIALS  OF  ENGINEERING. 

*  Bovey's  Strength  of  Materials  and  Theory  of  Structures 8vo, 

Burr's  Elasticity  and  Resistance  of  the  Materials  of  Engineering.    6th  Edition. 

Reset 8vo, 

Church's  Mechanics  of  Engineering 8vo, 

*  Greene's  Structural  Mechanics <?vo, 

Johnson's  Materials  of  Construction 8vo, 

Keep's  Cast  Iron 8vo, 

Lanza's  Applied  Mechanics 8vo, 

Martens's  Handbook  on  Testing  Materials.     (Henning.) 8vo, 

Maurer's  Technical  Mechanics 8vo, 

Merriman's  Mechanics  of  Materials 8vo, 

*  Strength  of  Materials i2mo, 

Metcalf 's  Steel.     A  Manual  for  Steel-users i2mo, 

Sabin's  Industrial  and  Artistic  Technology  of  Paints  and  Varnish 8vo, 

Smith's  Materials  of  Machines i2mo, 

Thurston's  Materials  of  Engineering 3  vols.,  8vo, 

Part  II.     Iron  and  Steel 8vo, 

Part  III.     A  Treatise  on  Brasses,  Bronzes,  and  Other  Alloys  and  their 

Constituents 8vo,    2  50 

Wood's  (De  V.)  Treatise  on  the  Resistance  of  Materials  and  an  Appendix  on 

the  Preservation  of  Timber 8vo,    2  00 

Elements  of  Analytical  Mechanics 8vo,    3  00 

Wood's  (M.  P.)  Rustless  Coatings:    Corrosion  and  Electrolysis  of  Iron  and 

Steel  8vo,    4  00 


STEAM-ENGINES  AND  BOILERS. 

Berry's  Temperature-entropy  Diagram i2mo,  1  25 

Carnot's  Reflections  on  the  Motive  Power  of  Heat.     (Thurston.) i2mo,  1  50 

Dawson's  "  Engineering  "  and  Electric  Traction  Pocket-book.  . .  .  i6mo,  mor.,  5  00 

Ford's  Boiler  Making  for  Boiler  Makers i8mo,  1  00 

Goss's  Locomotive  Sparks 8vo,  2  00 

Locomotive  Performance 8vo,  5  00 

Hemenway's  Indicator  Practice  and  Steam-engine  Economy 121110,  2  00 

14 


7 

50 

6 

00 

2 

50 

6 

00 

2 

50 

7 

50 

7 

50 

4 

00 

5 

00 

1 

00 

2 

00 

3 

00 

1 

00 

8 

00 

3 

50 

Hutton's  Mechanical  Engineering  of  Power  Plants 8vo,  5  00 

Heat  and  Heat-engines 8vo  5  00 

Kent's  Steam  boiler  Economy 8vo,  4  00 

Kneass's  Practice  and  Theory  of  the  Injector 8vo,  1   50 

MacCord's  Slide-valves 8vo,  2  00 

Meyer's  Modern  Locomotive  Construction 4to,  10  00 

Peabody's  Manual  of  the  Steam-engine  Indicator i2mo,  1   50 

Tables  of  the  Properties  of  Saturated  Steam  and  Other  Vapors    8vo,  1  00 

Thermodynamic  of  the  Steam-engine  and  Other  Heat-engines 8vo,  5  00 

Valve-gears  for  Steam-engines 8vo,  2  50 

Peabody  and  Miller's  Steam-boilers 8vo,  4  00 

Pray's  Twenty  Years  with  the  Indicator Large  8vo,  2  5c 

Pupin's  Thermodynamics  of  Reversible  Cycles  in  Gases  and  Saturated  Vapors. 

(Osterberg.) i2mo,  1   25 

Reagan's  Locomotives:    Simple,  Compound,  and  Electric.     New  Edition. 

Large  i2mo,  3   -o 

Rontgen's  Principles  of  Thermodynamics.     (Du  Bois.) 8vo,  5  o« 

Sinclair's  Locomotive  Engine  Running  and  Management i2mo,  2  00 

Smart's  Handbook  of  Engineering  Laboratory  Practice nmo,  2  50 

Snow's  Steam-boiler  Practice 8vo,  3  00 

Spangler's  Valve-gears 8vo,  2  50 

Notes  on  Thermodynamics 1 2mo,  1  00 

Spangler,  Greene,  and  Marshall's  Elements  of  Steam-engineering 8vo,  3  00 

Thomas's  Steam-turbines 8vo,  3  50 

Thurston's  Handy  Tables 8vo,  1  50 

Manual  of  the  Steam-engine 2  vols.,  8vo,  10  00 

Part  I.     History,  Structure,  and  Theory 8vo,  6  00 

Part  II.     Desisn,  Construction,  and  Operation 8vo,  6  00 

Handbook  of  Engine  and  Boiler  Trials,  and  the  Use  of  the  Indicator  and 

the  Prony  Brake 8vo,  5  00 

Stationary  Steam-engines 8vo,  2  50 

Steam-boiler  Explosions  in  Theory  and  in  Practice nmo,  1   50 

Manual  of  Steam-boilers,  their  Designs,  Construction,  and  Operation. 8vo,  5  00 

Wehrenfenning's  Analysis  and  Softening  of  Boiler  Feed-water  (Patterson)   8vo,  4  00 

Weisbach's  Heat,  Steam,  and  Steam-engines.     (Du  Bois.) 8vo,  5  00 

Whitham's  Steam-engine  Design 8vo,  5  00 

Wood's  Thermodynamics,  Heat  Motors,  and  Refrigerating  Machines.  ..8vo,  4  00 


MECHANICS   AND   MACHINERY. 

Barr's  Kinematics  of  Machinery 8vo,  2  50 

*  Bovey's  Strength  of  Materials  and  Theory  of  Structures   8vo,  7  50 

Chase's  The  Art  of  Pattern-making l2mo,  2  50 

Church's  Mechanics  of  Engineering 8vo,  6  00 

Notes  and  Examples  in  Mechanics 8vo,  2  00 

Compton's  First  Lessons  in   Metal-working i2mo,  1    50 

Compton  and  De  Groodt's  The  Speed  Lathe i2mo,  1   50 

Cromwell's  Treatise  on  Toothed  Gearing nmo,  1   50 

Treatise  on  Belts  and  Pulleys i2mo,  1   50 

Dana's  Text-book  of  Elementary  Mechanics  for  Colleges  and  Schools.  ,i2mo,  1   50 

Dingey's  Machinery  Pattern  Making i2mo,  2  00 

Dredge's   Record  of   the   Transportation   Exhibits  Building  of   the   World's 

Columbian  Exposition  of  1893 4to  half  morocco,  5  00 

Du  Bois's  Elementary  Principles  of  Mechanics: 

Vol.      I.     Kinematics 8vo,  3  50 

Vol.    II.     Statics 8vo.  4  00 

Mechanics  of  Engineering.     Vol.    I Small  4to,  7  50 

Vol.  II Small  4to,  10  00 

Durley's  Kinematics  of  Machines 8vo,  4  00 

15 


Fitzgerald's  Boston  Machinist i6mo,  i  oo 

Flather's  Dynamometers,  and  the  Measurement  of  Power i2mo,  3  00 

Rope  Driving i2mo,  2  00 

Goss's  Locomotive  Sparks 8vo,  2  00 

Locomotive  Performance 8vo,  5  00 

*  Greene's  Structural  Mechanics 8vo,  2  50 

Hall's  Car  Lubrication i2mo,  1  00 

Holly's  Art  of  Saw  Filing i8mo,  75 

James's  Kinematics  of  a  Point  and  the  Rational  Mechanics  of  a  Particle. 

Small  8vo,  2  00 

*  Johnson's  (W.  W.)  Theoretical  Mechanics i2mo,  3  00 

Johnson's  (L.  J.)  Statics  by  Graphic  and  Algebraic  Methods 8vo,  2  00 

Jones's  Machine  Design: 

Part    I.     Kinematics  of  Machinery 8vo,  1  50 

Part  II.     Form,  Strength,  and  Proportions  of  Parts 8vo,  3  00 

Kerr's  Power  and  Power  Transmission 8vo,  2  00 

Lanza's  Applied  Mechanics 8vo,  7  50 

Leonard's  Machine  Shop,  Tools,  and  Methods 8vo,  4  00 

*  Lorenz's  Modern  Refrigerating  Machinery.     (Pope,  Haven,  and  Dean.). 8vo,  4  00 
MacCord's  Kinematics;   or,  Practical  Mechanism 8vo,  5  00 

Velocity  Diagrams 8vo,  1  50 

*  Martin's  Text  Book  on  Mechanics,  Vol.  I,  Statics i2mo,  1   25 

Maurer's  Technical  Mechanics 8vo,  4  00 

Merriman's  Mechanics  of  Materials 8vo,  5  00 

*  Elements  of  Mechanics i2mo,  1  00 

*  Michie's  Elements  of  Analytical  Mechanics 8vo,  4  00 

*  Parshall  and  Hobart's  Electric  Machine  Design 4T0,  half  morocco,  12  50 

Reagan's  Locomotives :  Simple,  Compound,  and  Electric.     New  Edition. 

Large  i2mo,  3  00 

Reid's  Course  in  Mechanical  Drawing 8vo,  2  00 

Text-book  of  Mechanical  Drawing  and  Elementary  Machine  Design. 8vo,  3  00 

Richards's  Compressed  Air i2mo,  1  50 

Robinson's  Principles  of  Mechanism 8vo,  3  00 

Ryan,  Norris,  and  Hoxie's  Electrical  Machinery.     Vol.  1 8vo,  2  50 

Sanborn's  Mechanics:  Problems Large  i2mo,  1   50 

Schwamb  and  Merrill's  Elements  of  Mechanism 8vo,  3  00 

Sinclair's  Locomotive-engine  Running  and  Management i2mo,  2  00 

Smith's  (O.)  Press-working  of  Metals 8vo,  3  00 

Smith's  (A.  W.)  Materials  of  Machines nmo,  1  00 

Smith  (A.  W.)  and  Marx's  Machine  Design 8vo,  3  00 

Spangler,  Greene,  and  Marshall's  Elements  of  Steam-engineering.: 8vo,  3  00 

Thurston's  Treatise  on  Friction  and  Lost  Work  in    Machinery  and    Mill 

Work 8vo,  3  00 

Animal  as  a  Machine  and  Prime  Motor,  and  the  Laws  of  Energetics.  1 2mo ,  1  00 

Tillson's  Complete  Automobile  Instructor i6mo,  1  50 

Morocco,  2  00 

Warren's  Elements  of  Machine  Construction  and  Drawing 8vo,  7  50 

Weisbach's  Kinematics  and  Power  of  Transmission.   (Herrmann — Klein. ) .  8vo,  5  00 

Machinery  of  Transmission  and  Governors.      (Herrmann — Klein. ).8vo,  5  00 

Wood's  Elements  of  Analytical  Mechanics 8vo,  3  00 

Principles  of  Elementary  Mechanics i2mo,  1  25 

Turbines 8vo,  2  50 

The  World's  Columbian  Exposition  of  1893 4to,  1  00 

MEDICAL. 

De  Fursac's  Manual  of  Psychiatry.     (Rosanoff  and  Collins.) Large  i2mo,  2  50 

Ehrlich's  Collected  Studies  on  Immunity.     (Bolduan.) 8vo,  6  00 

Hammarsten's  Text-book  on  Physiological  Chemistry.     (Mandel.) 8vo,   4  00 

16 


Lassar-Cohn's  Practical  Urinary  Analysis.     CLorenz.) i2n-.o,  i   oo 

*  Pauli's  Physical  Chemistry  in  the  Service  of  Medicine.      (Fischer,  i          i2mo,  i    35 

*  Pozzi-Escot's  The  Toxins  and  Venoms  and  their  Antibodies.      (Cohn.  1.  i2mo,  1 

Rostoski's  Serum  Diagnosis.     (Bolduan.) i2mo,  1   00 

Salkowski's  Physiological  and  Pathological  Chemistry.     (Orndorff.).    .      8*vo,  2  50 

*  Satterlee's  Oatlines  of  Human  Embryology i2mo,  1   25 

Steel's  Treatise  on  the  Diseases  of  the  Dog 8vo,  3  50 

Von  Behring's  Suppression  of  Tuberculosis.     (Bolduan.) i2mo,  1   00 

Wassermann's  Immune  Sera1  Haemolysis,  Cytotoxins,  and  Precipitins.     ( Bol- 
duan.1   i2mo,cloth,  1  00 

Woodhull's  Notes  on  Military  Hygiene i6mo,  1   50 

*  Personal  Hygiene i2mo,  1   00 

Wulling's  An  Elementary  Course  in  Inorganic  Pharmaceutical  and  Medical 

Chemfstry nmo,  2  00 


METALLURGY. 

Egleston's  Metallurgy  of  Silver,  Gold,  and  Mercury: 

Vol.    I.     Silver 8vo,  7  50 

Vol.  II.     Gold  and  Mercury 8vo,  7  50 

Goesel's  Minerals  and  Metals:     A  Reference  Book i6mo,  mor.  3  00 

*  Iles's  Lead-smelting i2mo,  2  50 

Keep's  Cast  Iron 8vo,  2  50 

Kunhardt's  Practice  of  Ore  Dressing  in  Europe 8vo,  1  50 

Le  Chatelier's  High-temperature  Measurements.  (Boudouard — Burgess.")  12 mo,  3  00 

Metcalf's  SteeL     A  Manual  for  Steel-users i2mo,  2  00 

Miller's  Cyanide  Process i2mo,  1  00 

Minet's  Production  of  Aluminum  and  its  Industrial  Use.     (Waldo.). ...  i2mo,  2  50 

Robine  and  Lenglen's  Cyanide  Industry.     (Le  Clerc.) 8vo,  4  00 

Smith's  Materials  of  Machines i2mo,  1  00 

Thurston's  Materials  of  Engineering.     In  Three  Parts 8vo,  8  00 

Part    II.     Iron  and  Steel 8vo,  3  50 

Part  III.     A  Treatise  on  Brasses,  Bronzes,  and  Other  Alloys  and  their 

Constituents 8vo,  2  50 

Ulke's  Modern  Electrolytic  Copper  Refining 8vo,  3  00 


MINERALOGY. 

Barringer's  Description  of  Minerals  of  Commercial  Value.    Oblong,  morocco,  2  50 

Boyd's  Resources  of  Southwest  Virginia 8vo,  3  00 

Map  of  Southwest  Virignia. Pocket-book  form.  2  00 

Brush's  Manual  of  Determinative  Mineralogy.     (Penfield.) 8vo,  4  00 

Chester's  Catalogue  of  Minerals 8vo,  paper,  1  00 

Cloth,  i  25 

Dictionary  of  the  Names  of  Minerals 8vo,  3  50 

Dana's  System  of  Mineralogy Large  8vo,  half  leather,  12  50 

First  Appendix  to  Dana's  New  "  System  of  Mineralogy." Large  8vo,  1  00 

Text-book  of  Mineralogy 8vo,  4  00 

Minerals  and  How  to  Study  Them i2mo.  1  50 

Catalogue  of  American  Localities  of  Minerals Large  8vo,  1  00 

Manual  of  Mineralogy  and  Petrography i2mo  2  00 

Douglas's  Untechnical  Addresses  on  Technical  Subjects i2mo,  1  00 

Eakle's  Mineral  Tables 8vo,  1  25 

Egleston's  Catalogue  of  Minerals  and  Synonyms 8vo,  2  50 

Goesel's  Minerals  and  Metals :     A  Reference  Book 1  Ohio,  mor.  3  00 

Groth's  Introduction  to  Chemical  Crystallography  (Marshall) i2mo,  1  25 

17 


Iddings's  Rock  Minerals 8vo,  5  00 

Merrill's  Non-metallic  Minerals:   Their  Occurrence  and  Uses 8vo,  4  00 

*  Penfield's  Notes  on  Determinative  Mineralogy  and  Record  of  Mineral  Tests. 

8vo,  paper,  50 

*  Richards's  Synopsis  of  Mineral  Characters i2mo,  morocco,  1  25 

*  Ries's  Clays:  Their  Occurrence,  Properties,  and  Uses 8vo,  5  00 

Rosenbusch's    Microscopical   Physiography    of   the    Rock-making  Minerals. 

(Iddings.) 8vo,  5  00 

*  Tillman's  Text-book  of  Important  Minerals  and  Rocks 8vo,  2  00 


MINING. 

Boyd's  Resources  of  Southwest  Virginia 8vo,  3  00 

Map  of  Southwest  Virginia Pocket-book  form  2  00 

Douglas's  Untechnical  Addresses  on  Technical  Subjects i2mo,  I  00 

Eissler's  Modern  High  Explosives.      ...    R~~>  4  ">i 

Goesel's  Minerals  and  Metals :     A  Reference  Book i6mo,mor.  300 

Goodyear's  Coal-mines  of  the  Western  Coast  of  the  United  States i2mo,  2  50 

Ihlseng's  Manual  of  Mining 8vo,  5  00 

*  Iles's  Lead-smelting nmo,  2  50 

Kunhardt's  Practice  of  Ore  Dressing  in  Europe 8vo,  1  50 

Miller's  Cyanide  Process i2mo,  1  00 

O'Driscoll's  Notes  on  the  Treatment  of  Gold  Ores 8vo,  2  00 

Robine  and  Lenglen's  Cyanide  Industry.     (Le  Clerc.) 8vo,  4  00 

*  Walke's  Lectures  on  Explosives 8vo,  4  00 

Weaver's  Military  Explosives 8vo,  3  00 

Wilson's  Cyanide  Processes i2mo,  1  50 

Chlorination  Process i2mo,  1  50 

Hydraulic  and  Placer  Mining nmo,  2  00 

Treatise  on  Practical  and  Theoretical  Mine  Ventilation i2mo,  1  25 


SANITARY  SCIENCE. 

Bashore's  Sanitation  of  a  Country  House nmo,     1  00 

*  Outlines  of  Practical  Sanitation nmo,    1  25 

Folwell's  Sewerage.     (Designing,  Construction,  and  Maintenance.) 8vo,    3  00 

Water-supply  Engineering. 8vo,    4  00 

Fowler's  Sewage  Works  Analyses nmo,    2  00 

Fuertes's  Water  and  Public  Health nmo,     1  50 

Water-filtration  Works nmo,    2  50 

Gerhard's  Guide  to  Sanitary  House-inspection i6mo,    1  00 

Hazen's  Filtration  of  Public  Water-supplies 8vo,    3  00 

Leach's  The  Inspection  and  Analysis  of  Food  with  Special  Reference  to  State 

Control 8vo, 

Mason's  Water-supply.  ( Considered  principally  from  a  Sanitary  Standpoint)  8vo, 

Examination  of  Water.     (Chemical  and  Bacteriological.) nmo, 

*  Merriman's  Elements  of  Sanitary  Engineering 8vo, 

Ogden's  Sewer  Design nmo, 

Prescott  and  Winslow's  Elements  of  Water  Bacteriology,  with  Special  Refer- 
ence to  Sanitary  Water  Analysis nmo, 

*  Price's  Handbook  on  Sanitation nmo, 

Richards's  Cost  of  Food.     A  Study  in  Dietaries nmo, 

Cost  of  Living  as  Modified  by  Sanitary  Science nmo, 

Cost  of  Shelter nmo, 

18 


7 

50 

4 

00 

1 

25 

2 

00 

2 

00 

1 

25 

1 

5<* 

Richards  and  Woodman's  Air.   Water,  and   Food   from  a  Sanitary   Stand- 
point  8vo,  2  oo 

*  Richards  and  Williams's  The  Dietary  Computer 8vo.  i   50 

Rideal's  Sewage  and  Bacterial  Purification  of  Sewage 8vo,  4  00 

Turneaure  and  Russell's  Public  Water-supplies 8vo,  5  00 

Von  Behring's  Suppression  of  Tuberculosis.     (Bolduan.) i2mo,  1   00 

Whipple's  Microscopy  of  Drinking-water 8vo,  3  50 

Winton's  Microscopy  of  Vegetable  Foods 8vo,  7  50 

Woodhull's  Notes  on  Military  Hygiene i6mo,  1  50 

*  Personal  Hygiene i2mo,  1  00 


MISCELLANEOUS. 

Emmons's  Geological  Guide-book  of  the  Rocky  Mountain  Excursion  of  the 

International  Congress  of  Geologists Large  8vo,  1  50 

Ferrel's  Popular  Treatise  en  the  Winds 8vo,  4  00 

Gannett's  Statistical  Abstract  of  the  World   24010,  75 

Haines's  American  Railway  Management i2mo,  2  50 

Ricketts's  Eistory  of  Rensselaer  Polytechnic  Institute,  1 824-1 894.  .Small  8 vo,  3  00 

Rotherham's  Emphasized  New  Testament Large  8vo .  2  00 

The  World's  Columbian  Exposition  of  1893 4to,  1  00 

Winslow's  Elements  of  Applied  Microscopy nmo,  1  50 


HEBREW  AND  CHALDEE  TEXT-BOOKS. 

Green's  Elementary  Hebrew  Grammar nmo,  1  25 

Hebrew  Chrestomathy 8vo,  2  00 

Gesenius's  Hebrew  and  Chaldee  Lexicon  to  the  Old  Testament  Scriptures. 

(Tregelles.) Small  4to,  half  morocco,  5  00 

Letteris's  Hebrew  Bible 8vo,  2  25 

19 


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